FORBES.com, December 7, 2010, by Lauran Neergaard, BALTIMORE — This is no ordinary intensive care unit: Every doctor, nurse, friend or loved one must cover their clothes with a bright yellow gown and don purple gloves before entering a patient’s room so some scary germs don’t hitch a ride in or out.
It’s part of the University of Maryland Medical Center’s crackdown on hospital-spread infections, and Michael Anne Preas patrols the ICU like a cop on the beat to help keep bacteria in check.
You forgot your gloves, Preas leans in to tell a doctor-in-training who’s about to examine a man with a breathing tube. Startled, the resident immediately washes his hands and grabs a pair.
Peering at the IV tube inserted into another patient’s neck, Preas spots a different opening for bacteria: His long beard is messing up what should be an airtight seal. Let’s shave that spot and put in a new catheter, she tells the nurse.
Nor does a janitor escape Preas’ inspection. Yes, she put on clean gloves between collecting trash and moving carts that nurses will touch.
Infections caught at health care facilities are one of the nation’s leading causes of preventable death, claiming an estimated 99,000 lives a year. Yet chances are you’ve never heard of Preas’ job: She’s an infection preventionist, part of an evolution under way as hospitals are pushed to slash those rates or lose lucrative Medicare dollars.
“You have to be out and about,” says Preas, who with a team of four other specialists checks parts of this large Baltimore teaching hospital for infection-control steps, looking to identify the inevitable spots where fast-paced care can allow the bugs an entry. Doctors and nurses are under orders to heed their advice.
The program is unusual. There are only about 8,000 to 10,000 infection preventionists nationwide, and in most smaller hospitals they’re occupied with documenting infection statistics or advising doctors about specific pathogens, according to the Association for Professionals in Infection Control and Epidemiology.
But with some other steps, it’s starting to pay off: This surgical ICU has gone 24 weeks without a single case of one of the most insidious hospital infections, where bacteria infiltrate the bloodstream through that easy-to-contaminate IV catheter called a central line. Hospital-wide, those central line infections have dropped 70 percent in the past year.
“Every single nurse and doctor and staff member who touches a patient can either prevent or not prevent an infection from occurring,” says chief medical officer Dr. Jonathan Gottlieb.
Not too long ago, specialists like Preas were “prophets in the wilderness,” he says, struggling to advise about best practices but not typically at the bedside to see the barriers.
“We can say, ‘Do this, do this, do this,’ but we have to convince people to change,” adds Dr. Kerri Thom, an epidemiologist who accompanies Preas on her daily rounds.
With 1.7 million healthcare-acquired infections a year, adding $20 billion to the nation’s health bills, infections have long plagued hospitals. But they’re getting renewed attention as the federal government aims to cut certain types in half in the next few years, linking success to dollars. Already, Medicare has begun cutting payments to hospitals with high rates of certain infections, cuts that will increase by 2015 under the new health care law.
Part of the challenge: For every patient suffering an obvious infection, another five to 10 may carry the same bacteria into the hospital with no symptoms – germs on their skin or in their noses that can threaten the patient in the next room, or even the carrier himself if the bugs slip into the bloodstream through a surgical wound or catheter.
Hence the decision by the University of Maryland Medical Center to have every visitor to a surgical ICU room don a gown and gloves. Researchers found one dangerous germ, acinetobacter, is especially easy to spread – lurking on bed rails and IV pumps and other places that mean even workers not touching the patient could walk out contaminated.
“If we weren’t wearing them, it would be on our clothes,” Thom says of the protective gear, noting that infection specialists tend not to wear health care’s ubiquitous white lab coats.
Without frequent washing, “if you wear your lab coat everywhere you go, it becomes a walking germ,” Preas adds.
And some germs need a stronger attack than others: On this fall day, Preas tells ICU nurses to post new brown-colored warning signs on the rooms of people with diarrhea, a possible sign of an intestinal superbug named Clostridium difficile, or C-diff.
Health workers tend to use alcohol-based hand sanitizers that work well on most germs but won’t kill the fecal spores that spread C. diff, she explains. While there’s debate about the best approach, she advises the ICU nurses to wash hands with soap and water after removing their gloves and leaving those rooms – and to clean the room’s equipment with bleach.
EDITOR’S NOTE – Lauran Neergaard covers health and medical issues for The Associated Press in Washington.
People generally check into hospitals to get well, not to get sicker. But hospital-acquired infections have become a major problem in this country and worldwide. Now a new study is pointing a finger of blame at hospital housekeeping staff and their cleaning techniques.
Researchers in Canada used a lotion that glows under ultraviolet light to show that up to one-third of patient toilets are not properly cleaned. The scientists checked for the dangerous bacterium Clostridium difficile, which causes diarrhea and can lead to blood poisoning and death. Even 40% of the samples taken from the cleanest toilets contained C. difficile spores, suggesting the cleaning agents may not be working so well either. The study was published in BMC Infectious Diseases.
Last month, the Agency for Healthcare Research and Quality reported that C. difficile cases in hospital patients increased by 200% between 2000 and 2005. Though no one relishes the thought of unclean hospital bathrooms, the repercussions of clinging C. difficile germs are profound. The healthcare agency reports that patients with the infection (which results after previous antibiotic therapy suppresses the normal bacteria of the colon) were hospitalized almost three times longer than uninfected patients and had an in-hospital death rate of 9.5% compared with 2.1% overall.
— Shari Roan
Drawing: Paul Corio / For The Times
Gram-negative Pseudomonas aeruginosa bacteria (pink-red rods).
Gram-negative bacteria are those bacteria that do not retain crystal violet dye in the Gram staining protocol. Gram-positive bacteria will retain the crystal violet dye when washed in a decolorizing solution. In a Gram stain test, a counterstain (commonly safranin) is added after the crystal violet, coloring all Gram-negative bacteria a red or pink color. The test itself is useful in classifying two distinct types of bacteria based on structural differences in their cell walls.
Many species of Gram-negative bacteria are pathogenic, meaning they can cause disease in a host organism. This pathogenic capability is usually associated with certain components of Gram-negative cell walls, in particular the lipopolysaccharide (also known as LPS or endotoxin) layer. In humans, LPS triggers an innate immune response characterized by cytokine production and immune system activation. Inflammation is a common result of cytokine production, which can also produce host toxicity.
Gram-positive and -negative bacteria are chiefly differentiated by their cell wall structure.
The following characteristics are displayed by Gram-negative bacteria:
1. Cytoplasmic membrane
2. Thin peptidoglycan layer (which is present in much higher levels in Gram-positive bacteria)
3. Outer membrane containing lipopolysaccharide (LPS, which consists of lipid A, core polysaccharide, and O antigen) outside the peptidoglycan layer
4. Porins exist in the outer membrane, which act like pores for particular molecules
5. There is a space between the layers of peptidoglycan and the secondary cell membrane called the periplasmic space
6. The S-layer is directly attached to the outer membrane, rather than the peptidoglycan
7. If present, flagella have four supporting rings instead of two
8. No teichoic acids or lipoteichoic acids are present
9. Lipoproteins are attached to the polysaccharide backbone whereas in Gram-positive bacteria no lipoproteins are present
10. Most do not sporulate (Coxiella burnetti, which produces spore-like structures, is a notable exception)
The proteobacteria are a major group of Gram-negative bacteria, including Escherichia coli, Salmonella, and other Enterobacteriaceae, Pseudomonas, Moraxella, Helicobacter, Stenotrophomonas, Bdellovibrio, acetic acid bacteria, Legionella and alpha-proteobacteria as Wolbachia and many others. Other notable groups of Gram-negative bacteria include the cyanobacteria, spirochaetes, green sulfur and green non-sulfur bacteria.
Medically relevant Gram-negative cocci include three organisms, which cause a sexually transmitted disease (Neisseria gonorrhoeae), a meningitis (Neisseria meningitidis), and respiratory symptoms (Moraxella catarrhalis).
Medically relevant Gram-negative bacilli include a multitude of species. Some of them primarily cause respiratory problems (Hemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa), primarily urinary problems (Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens), and primarily gastrointestinal problems (Helicobacter pylori, Salmonella enteritidis, Salmonella typhi).
Gram negative bacteria associated with nosocomial infections include Acinetobacter baumanii, which cause bacteremia, secondary meningitis, and ventilator-associated pneumonia in intensive care units of hospital establishments.
One of the several unique characteristics of Gram-negative bacteria is the structure of the outer membrane. The outer leaflet of the membrane comprises a complex lipopolysaccharide whose lipid portion acts as an endotoxin. If endotoxin enters the circulatory system it causes a toxic reaction with the sufferer having a high temperature and respiration rate and a low blood pressure. This may lead to endotoxic shock, which may be fatal.
This outer membrane protects the bacteria from several antibiotics, dyes, and detergents which would normally damage the inner membrane or cell wall (peptidoglycan). The outer membrane provides these bacteria with resistance to lysozyme and penicillin. Fortunately, alternative medicinal treatments such as lysozyme with EDTA, and the antibiotic ampicillin have been developed to combat the protective outer membrane of some pathogenic Gram-negative organisms. Other drugs can be used, namely chloramphenicol, streptomycin, and nalidixic acid.
When someone coughs, germs become airborne
Rising Threat of Infections Unfazed by Antibiotics
The MRSA Bacteria
The New York Times, by Andrew Pollack — A minor-league pitcher in his younger days, Richard Armbruster kept playing baseball recreationally into his 70s, until his right hip started bothering him. Last February he went to a St. Louis hospital for what was to be a routine hip replacement.
By late March, Mr. Armbruster, then 78, was dead. After a series of postsurgical complications, the final blow was a bloodstream infection that sent him into shock and resisted treatment with antibiotics.
“Never in my wildest dreams did I think my dad would walk in for a hip replacement and be dead two months later,” said Amy Fix, one of his daughters.
Not until the day Mr. Armbruster died did a laboratory culture identify the organism that had infected him: Acinetobacter baumannii.
The germ is one of a category of bacteria that by some estimates are already killing tens of thousands of hospital patients each year. While the organisms do not receive as much attention as the one known as MRSA — for methicillin-resistant Staphylococcus aureus — some infectious-disease specialists say they could emerge as a bigger threat.
That is because there are several drugs, including some approved in the last few years, that can treat MRSA. But for a combination of business reasons and scientific challenges, the pharmaceuticals industry is pursuing very few drugs for Acinetobacter and other organisms of its type, known as Gram-negative bacteria. Meanwhile, the germs are evolving and becoming ever more immune to existing antibiotics.
“In many respects it’s far worse than MRSA,” said Dr. Louis B. Rice, an infectious-disease specialist at the Louis Stokes Cleveland V.A. Medical Center and at Case Western Reserve University. “There are strains out there, and they are becoming more and more common, that are resistant to virtually every antibiotic we have.”
The bacteria, classified as Gram-negative because of their reaction to the so-called Gram stain test, can cause severe pneumonia and infections of the urinary tract, bloodstream and other parts of the body. Their cell structure makes them more difficult to attack with antibiotics than Gram-positive organisms like MRSA.
Acinetobacter, which killed Mr. Armbruster, came to wide attention a few years ago in infections of soldiers wounded in Iraq.
Meanwhile, New York City hospitals, perhaps because of the large numbers of patients they treat, have become the global breeding ground for another drug-resistant Gram-negative germ, Klebsiella pneumoniae.
According to researchers at SUNY Downstate Medical Center, more than 20 percent of the Klebsiella infections in Brooklyn hospitals are now resistant to virtually all modern antibiotics. And those supergerms are now spreading worldwide.
Health authorities do not have good figures on how many infections and deaths in the United States are caused by Gram-negative bacteria. The Centers for Disease Control and Prevention estimates that roughly 1.7 million hospital-associated infections, from all types of bacteria combined, cause or contribute to 99,000 deaths each year.
But in Europe, where hospital surveys have been conducted, Gram-negative infections are estimated to account for two-thirds of the 25,000 deaths each year caused by some of the most troublesome hospital-acquired infections, according to a report released in September by health authorities there.
To be sure, MRSA remains the single most common source of hospital infections. And it is especially feared because it can also infect people outside the hospital. There have been serious, even deadly, infections of otherwise healthy athletes and school children.
By comparison, the drug-resistant Gram-negative germs for the most part threaten only hospitalized patients whose immune systems are weak. The germs can survive for a long time on surfaces in the hospital and enter the body through wounds, catheters and ventilators.
What is most worrisome about the Gram-negatives is not their frequency but their drug resistance.
“For Gram-positives we need better drugs; for Gram-negatives we need any drugs,” said Dr. Brad Spellberg, an infectious-disease specialist at Harbor-U.C.L.A. Medical Center in Torrance, Calif., and the author of “Rising Plague,” a book about drug-resistant pathogens. Dr. Spellberg is a consultant to some antibiotics companies and has co-founded two companies working on other anti-infective approaches. Dr. Rice of Cleveland has also been a consultant to some pharmaceutical companies.
Doctors treating resistant strains of Gram-negative bacteria are often forced to rely on two similar antibiotics developed in the 1940s — colistin and polymyxin B. These drugs were largely abandoned decades ago because they can cause kidney and nerve damage, but because they have not been used much, bacteria have not had much chance to evolve resistance to them yet.
“You don’t really have much choice,” said Dr. Azza Elemam, an infectious-disease specialist in Louisville, Ky. “If a person has a life-threatening infection, you have to take a risk of causing damage to the kidney.”
Such a tradeoff confronted Kimberly Dozier, a CBS News correspondent who developed an Acinetobacter infection after being injured by a car bomb in 2006 while on assignment in Iraq. After two weeks on colistin, Ms. Dozier’s kidneys began to fail, she recounted in her book, “Breathing the Fire.”
Even that dire tradeoff might not be available to some patients. Last year doctors at St. Vincent’s Hospital in Manhattan published a paper describing two cases of “pan-resistant” Klebsiella, untreatable by even the kidney-damaging older antibiotics. One of the patients died and the other eventually recovered on her own, after the antibiotics were stopped.
“It is a rarity for a physician in the developed world to have a patient die of an overwhelming infection for which there are no therapeutic options,” the authors wrote in the journal Clinical Infectious Diseases.
In some cases, antibiotic resistance is spreading to Gram-negative bacteria that can infect people outside the hospital.
Sabiha Khan, 66, went to the emergency room of a Chicago hospital on New Year’s Day suffering from a urinary tract and kidney infection caused by E. coli resistant to the usual oral antibiotics. Instead of being sent home to take pills, Ms. Khan had to stay in the hospital 11 days to receive powerful intravenous antibiotics.
This month, the infection returned, sending her back to the hospital for an additional two weeks.
Some patient advocacy groups say hospitals need to take better steps to prevent such infections, like making sure that health care workers frequently wash their hands and that surfaces and instruments are disinfected. And antibiotics should not be overused, they say, because that contributes to the evolution of resistance.
To encourage prevention, an Atlanta couple, Armando and Victoria Nahum, started the Safe Care Campaign after their 27-year-old son, Joshua, died from a hospital-acquired infection in October 2006.
Joshua, a skydiving instructor in Colorado, had fractured his skull and thigh bone on a hard landing. During his treatment, he twice acquired MRSA and then was infected by Enterobacter aerogenes, a Gram-negative bacterium.
“The MRSA they got rid of with antibiotics,” Mr. Nahum said. “But this one they just couldn’t do anything about.”
CNN.com — A new crop of drug-resistant superbugs is in our midst, and experts believe that they could rival the deadly superbug MRSA.
A new report from the Infectious Diseases Society of America says these superbugs are creeping onto the radar in hospitals across the country, and our ability to fight them is next to none.
Question: Are these new superbugs poised to be the next MRSA?
Dr. Sanjay Gupta, CNN Chief Medical News Correspondent: They just may be, according to that new report by the Infectious Diseases Society of America, but we can’t say that just yet. MRSA is still a much bigger problem.
First, let’s define what these superbugs are. They’re called “gram-negative” bacteria. They are extremely drug-resistant; they have long, complicated names like “acinetobacter baumanii” and “klebsiella pneumoniae.” Two important issues related to these bacteria: They are increasingly cropping up in hospitals, and they are nearly impossible to treat.
Dr. Gupta’s Blog: Here’s why you should be scared of superbugs
Question: Is this related to the Brazilian model who recently died from a bacterial infection?
Gupta: Yes. A gram-negative bacterial infection killed Brazilian model Mariana Bridi da Costa last month. She had her hands and feet amputated and kidneys removed to try to stem the infection’s spread before she died. Gram-negative bacteria are also responsible for a spate of infections among returning Iraq war vets.
We’ve talked a lot about MRSA — methicillin-resistant Staphlyococcus aureus — and the core issue there is that very few antibiotics can treat it. The biggest concern with gram-negative bacteria is, there are virtually no drugs to effectively treat them. One drug, Colistin, is the only option that sometimes works, but it is incredibly toxic — can cause kidney damage.
Q: So how do these infections spread?
Gupta: Gram-negative infections are spread almost exclusively in hospitals, whereas MRSA has escaped the hospital confines and can now be found in the community. But keep in mind that MRSA started in hospitals.
Doctors see gram-negative infections among patients who are already very ill. Might be babies in the NICU, very old patients, patients who’ve just had surgery, burn patients in the ICU, for example. Gram-negative bacteria can enter the body by way of catheters, IVs, ventilators or wounds.
Diplococci: usually characteristic of Neiseria spp., such as N. meningitidis
In addition, Moraxella spp. and Acinetobacter spp.are often diplococcal in morphology. Acinetobacter can be pleomorphic, and sometimes appear as Gram-positive cocci.
Coccobacilli: usually characteristic of Acinetobacter spp., which can be either Gram-positive or Gram-negative, and is often Gram-variable.
Thin rods: usually characteristic of enterobacteriaceae, such as E. Coli
Coccobacilli: usually characteristic of Haemophilus spp., such as H. influenzae
Curved: usually characteristic of Vibrio spp.; Campylobactor spp., such as V. cholerae
Thin needle shape: usually characteristic of Fusobacterium spp.
Spirochete Bacteria are this shape
Cocci Bacteria are a round shape
Bacteria are – A diverse group of ubiquitous microorganisms all of which consist of only a single cell that lacks a distinct nuclear membrane and has a cell wall of a unique composition (see illustration). Bacteria constitute the prokaryotic organisms of the living world. However, their classification is a controversial issue. It is now recognized, on the basis of differences in ribosomal RNA structure and nucleotide sequences (see molecular systematics), that prokaryotes form two evolutionarily distinct groups. Traditionally these were placed in a single kingdom, variously named Bacteria or Prokaryotae, which was divided into two subkingdoms: Archaea (archaebacteria), including the descendants of ancient bacterial groups; and Eubacteria, representing the vast majority of present-day bacteria. However, it is now recognized that these groups of prokaryotes are so distinct that they should each be raised to the status of domain: Archaea (the archaebacteria, containing a variable number of kingdoms) and Bacteria (containing a single kingdom, Eubacteria). Generally speaking, the term ‘bacteria’ includes both archaebacteria and eubacteria.
Bacteria can be characterized in a number of ways, for example by their reaction with Gram’s stain or on the basis of their metabolic requirements (e.g. whether or not they require oxygen: see aerobic respiration; anaerobic respiration) and shape. A bacterial cell may be spherical (see coccus), rodlike (see bacillus), spiral (see spirillum), comma-shaped (see vibrio), corkscrew-shaped (see spirochaete), or filamentous, resembling a fungal cell. The majority of bacteria range in size from 0.5 to 5 μm. Many are motile, bearing flagella, possess an outer slimy capsule, and produce resistant spores (see endospore). In general bacteria reproduce only asexually, by simple division of cells, but a few groups undergo a form of sexual reproduction (see conjugation). Bacteria are largely responsible for decay and decomposition of organic matter, producing a cycling of such chemicals as carbon (see carbon cycle), oxygen, nitrogen (see nitrogen cycle), and sulphur (see sulphur cycle). A few bacteria obtain their food by means of photosynthesis, including the Cyanobacteria; some are saprotrophs; and others are parasites, causing disease. The symptoms of bacterial infections are produced by toxins.
Bacteria are mostly unicellular (single-celled) organisms that lack chlorophyll and are among the smallest living things on Earth—only viruses are smaller. Multiplying rapidly under favorable conditions, bacteria can aggregate into colonies of millions or even billions of organisms within a space as small as a drop of water.
The Dutch merchant and amateur scientist Anton van Leeuwenhoek (1632–1723) was the first to observe bacteria and other microorganisms. Using single-lens microscopes of his own design, he described bacteria and other microorganisms (calling them “animacules”) in a series of letters to the Royal Society of London between 1674 and 1723.
Bacteria are classified as prokaryotes. Broadly, this taxonomic ranking reflects the fact that the genetic material of bacteria is contained in a single, circular chain of deoxyribonucleic acid (DNA) that is not enclosed within a nuclear membrane. The word prokaryote is derived from Greek meaning “prenucleus.” Moreover, the DNA of prokaryotes is not associated with the special chromosome proteins called histones, which are found in higher organisms. In addition, prokaryotic cells lack other membrane-bounded organ-elles, such as mitochondria. Prokaryotes belong to the kingdom Monera. Some scientists have proposed splitting this designation into the kingdoms Eubacteria and Archaebacteria. Eubacteria, or true bacteria, consist of more common species, while Archaebacteria (with the prefix archae—meaning ancient) represent microorganisms that are bacteria-like in appearance that inhabit very hostile environments. Scientists believe the latter microorganisms are most closely related to the bacteria that lived when Earth was very young. Examples of archaebacteria are halophiles, which live in extremely salty environments, and thermophiles, which can tolerate and even thrive in near boiling waters of geysers and geothermal vents of the ocean floor.
Characteristics of bacteria
Although all bacteria share certain structural, genetic, and metabolic characteristics, important biochemical differences exist among the many species of bacteria. These differences permit bacteria to live in many different, and sometimes extreme, environments. For example, some bacteria recycle nitrogen and carbon from decaying organic matter, then release these gases into the atmosphere to be reused by other living things. Other bacteria cause diseases in humans and animals, help digest sewage in treatment plants, or produce the alcohol in wine, beer, and liquors. Still others are used by humans to break down toxic waste chemicals in the environment, a process called bioremediation.
The cytoplasm of all bacteria is enclosed within a cell membrane surrounded by a rigid cell wall whose polymers, with few exceptions, include peptidoglycans—large, structural molecules made of protein carbohydrate.
Some bacteria can also secrete a viscous, gelatinous polymer (called the glycocalyx) on their cell surfaces. This polymer, composed either of polysaccharide, polypeptide, or both, is called a capsule when it occurs as an organized layer firmly attached to the cell wall. Capsules increase the disease-causing ability (virulence) of bacteria by inhibiting immune system cells called phagocytes from engulfing them. One such bacterium, Streptococcus pneumoniae, is the cause of pneumonia.
The shape of bacterial cells are classified as spherical (coccus), rodlike (bacillus), spiral (spirochete), helical (spirilla) and comma-shaped (vibrio) cells. Many bacilli and vibrio bacteria have whiplike appendages (called flagella) protruding from the cell surface. Flagella are composed of tight, helical rotors made of chains of globular protein called flagellin, and act as tiny propellers, making the bacteria very mobile.
Flagella may be arranged in any of four ways, depending on the species of bacteria. There is the monotrichous condition (single flagellum at one end), the amphitrichous (single flagellum at each end of the bacterium), the lophotrichous (two or more flagella at either or both ends of the bacterium), and the peritrichous condition (flagella distributed over the entire cell).
Spirochetes are spiral-shaped bacteria that live in contaminated water, sewage, soil and decaying organic matter, as well as inside humans and animals. Spirochetes move by means of axial filaments, which consist of bundles of fibrils arising at each end of the cell beneath an outer sheath. The fibrils, which spiral around the cell, rotate, causing an opposite movement of the outer sheath that propels the spirochetes forward, like a turning corkscrew. The best known spirochete is Treponema pallidum, the organism that causes syphilis.
On the surface of some bacteria are short, hairlike, proteinaceous projections that may arise at the ends of the cell or over the entire surface. These projections, called fimbriae, let the bacteria adhere to surfaces. For example, fimbriae on the bacterium Neisseria gonorrhoea, which causes gonorrhea, allow these organisms to attach to mucous membranes.
Other proteinaceous projections, called pili, occur singly or in pairs, and join pairs of bacteria together, facilitating transfer of DNA between them.
During periods of harsh environmental conditions some bacteria, such as those of the genera Clostridium and Bacillus, produce within themselves a dehydrated, thick-walled endospore. These endo-spores can survive extreme temperatures, dryness, and exposure to many toxic chemicals and to radiation. Endospores can remain dormant for long periods (hundreds of years in some cases) before being reactivated by the return of favorable conditions.
A primitive form of exchange of genetic material between bacteria involving plasmids does occur. Plasmids are small, circular, extrachromosomal DNA molecules that are capable of replication and are known to be capable of transferring genes among bacteria. For example, resistance plasmids carry genes for resistance to antibiotics from one bacterium to another, while other plasmids carry genes that confer pathogenicity. In addition, the transfer of genes via bacteriophages—viruses that specifically parasitize bacteria—also serves as a means of genetic recombination. Corynebacterium diphtheriae, for example, produces the diphtheria toxin only when infected by a phage that carries the diphtherotoxin gene.
The above examples of genetic information exchange between bacterial cells occurs regularly in nature. This natural exchange, or lateral gene transfer, can be mimicked artificially in the laboratory. Bioengineering uses sophisticated techniques to purposely transfer DNA from one organism to another in order to give the second organism some new characteristic it did not have previously. For example, in a process called transformation, antibiotic-susceptible bacteria that are induced to absorb manipulated plasmids placed in their environment, can acquire resistance to that antibiotic substance due to the new genes they have incorporated. Similarly, in a process called transfection, specially constructed viruses are used to artificially inject bioengineered DNA into bacteria, giving infected cells some new characteristic.
Bacteria synthesize special DNA-cutting enzymes (known as restriction enzymes) that destroy the DNA of phages that do not normally infect them. Purified restriction enzymes are used in the laboratory to slice pieces of DNA from one organism and insert them into the genetic material of another organism as mentioned above.
The term “bacterial growth” generally refers to growth of a population of bacteria, rather than of an individual cell. Individual cells usually reproduce asexually by means of binary fission, in which one cell divides into two cells. Thus, bacterial growth of the population is a geometric progression of numbers of cells, with division occurring in regular intervals, called generation time, ranging from 15 minutes to 16 hours, depending upon the type of bacterium. In addition, some filamentous bacteria (actinomycetes) reproduce by producing chains of spores at their tips, while other filamentous species fragment into new cells.
Under ideal conditions, the growth of a population of bacteria occurs in several stages termed lag, log, stationary, and death. During the lag phase, active metabolic activity occurs involving synthesis of DNA and enzymes, but no growth. Geometric population growth occurs during the log, or exponential phase, when metabolic activity is most intense and cell reproduction exceeds cell death. Following the log phase, the growth rate slows and the production of new cells equals the rate of cell death. This period, known as the stationary phase, involves the establishment of an equilibrium in population numbers and a slowing of the metabolic activities of individual cells. The stationary phase reflects a change in growing condition—for example, a lack of nutrients and/or the accumulation of waste products.
When the rate of cell deaths exceeds the number of new cells formed, the population equilibrium shifts to a net reduction in numbers and the population enters the death phase, or logarithmic decline phase. The population may diminish until only a few cells remain, or the population may die out entirely.
The physical and chemical requirements for growth can vary widely among different species of bacteria, and some are found in environments as extreme as cold polar regions and hot, acid springs.
In general, the physical requirements for bacteria include proper temperature, pH, and osmotic pressure. Most bacteria thrive only within narrow ranges of these conditions, however extreme those ranges may be.
The lowest temperature at which a particular species will grow is the minimum growth temperature, while the maximum growth temperature is the highest temperature at which they will grow. The temperature at which their growth is optimal is called the optimum growth temperature. In general, the maximum and minimum growth temperatures of any particular type of bacteria are about 30°F (–1°C) apart.
Most bacteria thrive at temperatures at or around that of the human body 98.6°F (37°C), and some, such as Escherichia coli, are normal parts of the human intestinal flora. These organisms are mesophiles (moderate-temperature-loving), with an optimum growth temperature between 77°F (25°C) and 104°F (40°C). Mesophiles have adapted to thrive in temperatures close to that of their host.
Psychrophiles, which prefer cold temperatures, are divided into two groups. One group has an optimal growth temperature of about 59°F (15°C), but can grow at temperatures as low as 32°F (0°C). These organisms live in ocean depths or Arctic regions. Other psychrophiles that can also grow at 32°F (0°C) have an optimal growth temperature between 68°F (20°C) and 86°F (30°C). These organisms, sometimes called psychrotrophs, are often those associated with food spoilage under refrigeration.
Thermophiles thrive in very hot environments, many having an optimum growth temperature between 122°F (50°C) and 140°F (60°C), similar to that of hot springs in Yellowstone National Park. Such organisms thrive in compost piles, where temperatures can rise as high as 140°F (60°C). Extreme thermophiles grow at temperatures above 195°F (91°C). Along the sides of hydrothermal vents on the ocean bottom 217 mi (350 km) north of the Galapagos Islands, for example, bacteria grow in temperatures that can reach 662°F (350°C).
Like temperature, pH also plays a role in determining the ability of bacteria to grow or thrive in particular environments. Most commonly, bacteria grow optimally within a narrow range of pH between 6.7 and 7.5.
Acidophiles, however, prefer acidic conditions. For example, Thiobacillus ferrooxidans, which occurs in drainage water from coal mines, can survive at pH 1. Other bacteria, such as Vibrio cholera, the cause of cholera, can thrive at a pH as high as 9.0.
Osmotic pressure is another limiting factor in the growth of bacteria. Bacteria are about 80-90% water; they require moisture to grow because they obtain most of their nutrients from their aqueous environment.
Cell walls protect prokaryotes against changes in osmotic pressure over a wide range. However, sufficiently hypertonic media at concentrations greater than those inside the cell (such as 20% sucrose) cause water loss from the cell by osmosis. Fluid leaves the bacteria causing the cell to contract, which, in turn, causes the cell membrane to separate from the overlying cell wall. This process of cell shrinkage is called plasmolysis.
Because plasmolysis inhibits bacterial cell growth, the addition of salts or other solutes to a solution inhibits food spoilage by bacteria, as occurs when meats or fish is salted.
Some types of bacteria, called extreme or obligate halophiles, are adapted to—and require—high salt concentrations, such as found in the Dead Sea, where salt concentrations can reach 30%. Facultative halophiles do not require high salt environments to survive, but are capable of tolerating these conditions. Halophiles can grow in salt concentrations up to 2%, a level that would inhibit the growth of other bacteria. However, some facultative halophiles, such as Halobacterium halobium grow in salt lakes, salt flats, and other environments where the concentration of salts is up to seven times greater than that of the oceans.
When bacteria are placed in hypotonic media with concentrations weaker than the inside of the cell, water tends to enter by osmosis. The accumulation of this water causes the cell to swell and then to burst, a process called osmotic lysis.
Carbon, nitrogen, and other growth factors
In addition to water and the correct salt balance, bacteria also require a wide variety of elements, especially carbon, hydrogen, and nitrogen, sulfur and phosphorus, potassium, iron, magnesium, and calcium. Growth factors, such as vitamins and pyrimi-dines and purines (the building blocks of DNA), are also necessary.
Carbon is the fundamental building block of all the organic compounds needed by living things, including nucleic acids, carbohydrates, proteins, and fats.
Chemoheterotrophs are bacteria that use organic compounds such as proteins, carbohydrates, and lipids as their carbon source, and which use electrons from organic compounds as their energy source. Most bacteria (as well as all fungi, protozoans and animals) are chemoheterotrophs. Chemoautotrophs (for example hydrogen, sulfur, iron, and nitrifying bacteria) use carbon dioxide as their carbon source and electrons from inorganic compounds as their energy source.
Saprophytes are heterotrophs that obtain their carbon from decaying dead organic matter. Many different soil bacteria release plant nitrogen as ammonia (ammonification). Other bacteria, the Nitrosomonas, convert ammonia to nitrite, while Nitrobacter convert nitrite to nitrate. Other bacteria, especially Pseudomonas, convert nitrate to nitrogen gas. These bacteria complement the activity of nitrogen-fixing bacteria (for example, Rhizobium), which fix nitrogen from the atmosphere and make it available to leguminous plants, and Azotobacter, which are also found in fresh and marine waters. Together, the activity of these bacteria underlies the nitrogen cycle, by which the gas is taken up by living organisms, used to make proteins and other organic compounds, returned to the soil during decay, then released into the atmosphere to be reused by living things.
Phototrophs use light as their primary source of energy, but may differ in their carbon sources. Photoheterotrophs (purple nonsulfur and green non-sulfur bacteria) use organic compounds as their carbon source, while photoautotrophs (for example, photosynthetic green sulfur and purple sulfur bacteria) use carbon dioxide as a source of carbon.
Aerobic and anaerobic bacteria
Oxygen may or may not be a requirement for a particular species of bacteria, depending on the type of metabolism used to extract energy from food (aerobic or anaerobic). In all cases, the initial breakdown of glucose to pyruvic acid occurs during glycolysis, which produces a net gain of two molecules of the energy-rich moleculeadenosine triphosphate (ATP).
Aerobic bacteria use oxygen to break down pyruvic acid, releasing much more ATP than is produced during glycolysis during the process known as aerobic respiration. In addition, aerobic bacteria have enzymes such as superoxide dismutase capable of breaking down toxic forms of oxygen, such as super-oxide free radicals, which are also formed by aerobic respiration.
During aerobic respiration, enzymes remove electrons from the organic substrate and transfer them to the electron transport chain, which is located in the membrane of the mitochondrion. The electrons are transferred along a chain of electron carrier molecules. At the final transfer position, the electrons combine with atoms of oxygen—the final electron acceptor— which in turn combines with protons (H+) to produce water molecules. Energy, in the form of ATP, is also made here. Along the chain of electron carriers, protons that are pumped across the mitochondrial membrane re-enter the mitochondrion. This flow of electrons across the membrane fuels oxidative phosphorylation, the chemical reaction that adds a phosphate group to adenosine diphosphate (ADP) to produce ATP.
Obligate aerobes must have oxygen in order to live. Facultative aerobes can also exist in the absence of oxygen by using fermentation or anaerobic respiration. Anaerobic respiration and fermentation occur in the absence of oxygen, and produce substantially less ATP than aerobic respiration.
Anaerobic bacteria use inorganic substances other than oxygen as a final electron acceptor. For example, Pseudomonas and Bacillus reduce nitrate ion (NO3–) to nitrite ion (NO2–), nitrous oxide (N2 O) or nitrogen gas (N2). Clostridium species, which include those that cause tetanus and botulism, are obligate anaerobes. That is, they are not only unable to use molecular oxygen to produce ATP, but are harmed by toxic forms of oxygen formed during aerobic respiration. Unlike aerobic bacteria, obligate anaerobes lack the ability synthesize enzymes to neutralize these toxic forms of oxygen.
The role of bacteria in fermentation
Fermentation bacteria are anaerobic, but use organic molecules as their final electron acceptor to produce fermentation end-products. Streptococcus, Lactobacillus, and Bacillus, for example, produce lactic acid, while Escherichia and Salmonella produce ethanol, lactic acid, succinic acid, acetic acid, CO2, and H2.
Fermenting bacteria have characteristic sugar fermentation patterns, i.e., they can metabolize some sugars but not others. For example, Neisseria meningitidis ferments glucose and maltose, but not sucrose and lactose, while Neisseria gonorrhoea ferments glucose, but not maltose, sucrose or lactose. Such fermentation patterns can be used to identify and classify bacteria.
During the 1860s, the French microbiologist Louis Pasteur (1822–95) studied fermenting bacteria. He demonstrated that fermenting bacteria could contaminate wine and beer during manufacturing, turning the alcohol produced by yeast into acetic acid (vinegar). Pasteur also showed that heating the beer and wine to kill the bacteria preserved the flavor of these beverages. The process of heating, now called pasteurization in his honor, is still used to kill bacteria in some alcoholic beverages, as well as milk.
Pasteur described the spoilage by bacteria of alcohol during fermentation as being a “disease” of wine and beer. His work was thus vital to the later idea that human diseases could also be caused by microorganisms, and that heating can destroy them.
Identifying and classifying bacteria
The most fundamental technique for classifying bacteria is the gram stain, developed in 1884 by Danish scientist Christian Gram (1853–1938). It is called a differential stain because it differentiates among bacteria and can be used to distinguish among them, based on differences in their cell wall.
In this procedure, bacteria are first stained with crystal violet, then treated with a mordant—a solution that fixes the stain inside the cell (e.g., iodine-KI mixture). The bacteria are then washed with a decolorizing agent, such as alcohol, and counterstained with safranin, a light red dye.
The walls of gram-positive bacteria (for example, Staphylococcus aureus ) have more peptidoglycans (the large molecular network of repeating disaccharides attached to chains of four or five amino acids) than do gram-negative bacteria. Thus, gram-positive bacteria retain the original violet dye and cannot be counterstained.
Gram-negative bacteria (e.g., Escherichia coli ) have thinner walls, containing an outer layer of lipopolysaccharide, which is disrupted by the alcohol wash. This permits the original dye to escape, allowing the cell to take up the second dye, or counterstain. Thus, gram-positive bacteria stain violet, and gram-negative bacteria stain pink.
The gram stain works best on young, growing populations of bacteria, and can be inconsistent in older populations maintained in the laboratory.
Microbiologists have accumulated and organized the known characteristics of different bacteria in a reference book called Bergey’s Manual of Systematic Bacteriology (the first edition of which was written primarily by David Hendricks Bergey of the University of Pennsylvania in 1923).
The identification schemes of Bergey’s Manual are based on morphology (e.g., coccus, bacillus), staining (gram-positive or negative), cell wall composition (e.g., presence or absence of peptidoglycan), oxygen requirements (e.g., aerobic, facultatively anaerobic) and biochemical tests (e.g., which sugars are aerobically metabolized or fermented).
In addition to the gram stain, other stains include the acid-fast stain, used to distinguish Mycobacterium species (for example, Mycobacterium tuberculosis, the cause of tuberculosis); endospore stain, used to detect the presence of endospores; negative stain, used to demonstrate the presence of capsules; and flagella stain, used to demonstrate the presence of flagella.
Another important identification technique is based on the principles of antigenicity—the ability to stimulate the formation of antibodies by the immune system. Commercially available solutions of antibodies against specific bacteria (antisera) are used to identify unknown organisms in a procedure called a slide agglutination test. A sample of unknown bacteria in a drop of saline is mixed with antisera that has been raised against a known species of bacteria. If the antisera causes the unknown bacteria to clump (agglutinate), then the test positively identifies the bacteria as being identical to that against which the antisera was raised. The test can also be used to distinguish between strains, slightly different bacteria belonging to the same species.
Phage typing, like serological testing, identifies bacteria according to their response to the test agent, in this case viruses. Phages are viruses that infect specific bacteria. Bacterial susceptibility to phages is determined by growing bacteria on an agar plate, to which solutions of phages that infect only a specific species of bacteria are added. Areas that are devoid of visible bacterial growth following incubation of the plate represent organisms susceptible to the specific phages.
Because a specific bacterium might be susceptible to infection by two or more different phages, it may be necessary to perform several tests to definitively identify a specific bacterium.
The evolutionary relatedness of different species can also be determined by laboratory analysis. For example, analysis of the amino acid sequences of proteins from different bacteria disclose how similar the proteins are. In turn, this reflects the similarity of the genes coding for these proteins.
Protein analysis compares the similarity or extent of differences between the entire set of protein products of each bacterium. Using a technique called electrophoresis, the entire set of proteins of each bacterium is separated according to size by an electrical charge applied across gel. The patterns produced when the gel is stained to show the separate bands of proteins reflects the genetic makeup, and relatedness, of the bacteria.
The powerful techniques of molecular biology have given bacteriologists other tools to determine the identity and relatedness of bacteria.
Taxonomists interested in studying the relatedness of bacteria compare the ratio of nucleic acid base pairs in the DNA of microorganisms, that is, the number of guanosine-cytosine pairs (G-C pairs) in the DNA. Because each guanosine on a double-stranded molecule of DNA has a complementary cyto-sine on the opposite strand, comparing the number of G-C pairs in one bacterium, with that in another bacterium, provides evidence for the extent of their relatedness.
Determining the percentage of G-C pairs making up the DNA also discloses the percentage of adenosine-thymine (A-T)—the other pair of complementary nucleic acids making up DNA (100% — [% G-C] = % A-T).
The closer the two percentages are, the more closely related the bacteria may be, although other lines of evidence are needed to make a definitive determination regarding relationships.
The principle of complementarity is also used to identify bacteria by means of nucleic acid hybridization. The technique assumes that if two bacteria are closely related, they will have long stretches of identical DNA. First, one bacterium’s DNA is isolated and gently heated to break the bonds between the two complementary strands. Specially prepared DNA probes representing short segments of the other organism’s DNA are added to this solution of single-stranded DNA. The greater degree to which the probes combine with (hybridize) complementary stretches of the single stranded DNA, the greater the relatedness of the two organisms.
In addition to helping bacteriologists better classify bacteria, the various laboratory tests are valuable tools for identifying disease-causing organisms. This is especially important when physicians must determine which antibiotic or other medication to use to treat an infection.
Bacteria and disease
The medical community did not accept the concept that bacteria can cause disease until well into the nineteenth century. Joseph Lister (1827–1912), an English surgeon, applied the so-called “germ theory” to medical practice in the 1860s. Lister soaked surgical dressing in carbolic acid (phenol), which reduced the rate of post-surgical infections so dramatically that the practice spread.
In 1876, the German physician Robert Koch (1843–1910) identified Bacillus anthracis as the cause of anthrax, and in so doing, developed a series of laboratory procedures for proving that a specific organism can cause a specific disease. These procedures, called Koch’s postulates, are still generally valid. Briefly, they state that, to prove an organism causes a specific disease, the investigator must systematically:
- find the same pathogenic microorganism in every case of the disease;
- isolate the pathogen from the diseased patient or experimental animal and grow it in pure culture;
- demonstrate that the pathogen from the pure culture causes the disease when it is injected into a healthy laboratory animal, and;
- isolate the pathogen from the inoculated animal and demonstrate that it is the original organism injected into the animal.
The ability to isolate, study, and identify bacteria has greatly enhanced the understanding of their disease-causing role in humans and animals, and the subsequent development of treatments. Part of that understanding derives from the realization that since bacteria are ubiquitous and are found in large numbers in and on humans, they can cause a wide variety of diseases.
The skin and the nervous, cardiovascular, respiratory, digestive, and genitourinary systems are common sites of bacterial infections, as are the eyes and ears.
The skin is the body’s first line of defense against infection by bacteria and other microorganisms, although it supports enormous numbers of bacteria itself, especially Staphylococcus and Streptococcus species. Sometimes these bacteria are only dangerous if they enter a break in the skin or invade a wound, for example, the potentially fatal staphylococcal toxic shock syndrome. Among other common bacterial skin ailments are acne, caused by Propionibacterium acnes and superficial infection of the outer ear canal, caused by Pseudomonas aeruginosa.
Among the neurological diseases are meningitis, an inflammation of the brain’s membranes caused by Neisseria meningitidis and Hemophilus influenzae.
Many medically important bacteria produce toxins, poisonous substances that have effects in specific areas of the body. Exotoxins are proteins produced during bacterial growth and metabolism and released into the environment. Most of these toxin-producing bacteria are gram positive.
Among the gram positive toxin-producing bacteria are Clostridium tetani, which causes tetanus, an often fatal paralytic disease of muscles; Clostridium botulinum, which causes botulism, a form of potentially lethal food poisoning; and Staphylococcus aureus, which also causes a form of food poisoning (gastroenteritis).
Most gram-negative bacteria (for example, Salmonella typhi, the cause of typhoid fever) produce endotoxins, toxins that are part of the bacterial cell wall.
As the role of bacteria in causing disease became understood, entire industries developed that addressed the public health issues of these diseases.
As far back as 1810, the French confectioner Nicholas Appert (1750–1841) proved that food stored in glass bottles and heated to high temperatures could be stored for long periods of time without spoiling. Appert developed tables that instructed how long such containers should be boiled, depending upon the type of food and size of the container. Today, the food preservation industry includes not only canning, but also freezing and freeze-drying. An important benefit to food preservation is the ability to destroy potentially lethal contamination by Clostridium botulinum spores.
Even as concepts of prevention of bacterial diseases were being developed, scientists were looking for specific treatments. Early in the twentieth century, the German medical researcher Paul Ehrlich (1854–1915) theorized about producing a “magic bullet” that would destroy pathogenic organisms without harming the host.
In 1928, the discovery by Scottish bacteriologist Alexander Fleming (1881–1955) that the mold Penicillium notatum inhibited growth of Staphylococcus aureus ushered in the age of antibiotics. Subsequently, English scientists Howard Florey (1898–1968) and Ernst Chain (1906–79), working at Oxford University in England, demonstrated the usefulness of penicillin, the antibacterial substance isolated from P. notatum in halting growth of this bacterium. This inhibitory effect of penicillin on bacteria is an example of antibiosis, and from this term is derived the word antibiotic, which refers to a substance produced by microorganisms that inhibits other microorganisms.
Beginning in the 1930s, the development of synthetic antibacterial compounds called sulfa drugs further stimulated the field of antibacterial drug research. The many different anti-bacterial drugs available today work in a variety of ways, such as the inhibition of synthesis of cell walls, of proteins, or of DNA or RNA.
As of 2006 medical science and the multi-billion dollar pharmaceutical industry are facing the problem of bacterial resistance to drugs, even as genetically engineered bacteria are being used to produce important medications for humans.
Bacteria have been designed to be adaptable. Their surrounding layers and the genetic information for these and other structures associated with a bacterium are capable of alteration. Some alterations are reversible, disappearing when the particular pressure is lifted. Other alterations are maintained and can even be passed on to succeeding generations of bacteria.
The first antibiotic was discovered in 1929. Since then, a myriad of naturally occurring and chemically synthesized antibiotics have been used to control bacteria. Introduction of an antibiotic is frequently followed by the development of resistance to the agent. Resistance is an example of the adaptation of the bacteria to the antibacterial agent.
Antibiotic resistance can develop swiftly. For example, resistance to penicillin (the first antibiotic discovered) was recognized almost immediately after introduction of the drug. As of the mid-1990s, almost 80% of all strains of Staphylococcus aureus were resistant to penicillin. Meanwhile, other bacteria remain susceptible to penicillin. An example is provided by Group A Streptococcus pyogenes, another gram-positive bacteria.
The adaptation of bacteria to an antibacterial agent such as an antibiotic can occur in two ways. The first method is known as inherent (or natural) resistance. Gram-negative bacteria are often naturally resistant to penicillin, for example. This is because these bacteria have another outer membrane, which makes the penetration of penicillin to its target more difficult. Sometimes when bacteria acquire resistance to an antibacterial agent, the cause is a membrane alteration that has made the passage of the molecule into the cell more difficult.
The second category of adaptive resistance is called acquired resistance. This resistance is almost always due to a change in the genetic make-up of the bacterial genome. Acquired resistance can occur because of mutation or as a response by the bacteria to the selective pressure imposed by the antibacterial agent. Once the genetic alteration that confers resistance is present, it can be passed on to subsequent generations. Acquired adaptation and resistance of bacteria to some clinically important antibiotics has become a great problem in the last decade of the twentieth century.
Bacteria adapt to other environmental conditions as well. These include adaptations to changes in temperature, pH, concentrations of ions such as sodium, and the nature of the surrounding support. An example of the latter is the response shown by Vibrio parahaemolyticus to growth in a watery environment versus a more viscous environment. In the more viscous setting, the bacteria adapt by forming what are called swarmer cells. These cells adopt a different means of movement, which is more efficient for moving over a more solid surface. This adaptation is under tight genetic control, involving the expression of multiple genes.
Bacteria react to a sudden change in their environment by expressing or repressing the expression of a whole lost of genes. This response changes the properties of both the interior of the organism and its surface chemistry. A well-known example of this adaptation is the so-called heat shock response of Escherichia coli. The name derives from the fact that the response was first observed in bacteria suddenly shifted to a higher growth temperature.
One of the adaptations in the surface chemistry of Gram-negative bacteria is the alteration of a molecule called lipopolysaccharide. Depending on the growth conditions or whether the bacteria are growing on an artificial growth medium or inside a human, as examples, the lipopolysaccharide chemistry can become more or less water-repellent. These changes can profoundly affect the ability of antibacterial agents or immune components to kill the bacteria.
Another adaptation exhibited by Vibrio parahaemolyticus, and a great many other bacteria as well, is the formation of adherent populations on solid surfaces. This mode of growth is called a biofilm. Adoption of a biofilm mode of growth induces a myriad of changes, many involving the expression of previously unexpressed genes. In addition, de-activation of actively expressing genes can occur. Furthermore, the pattern of gene expression may not be uniform throughout the biofilm. Bacteria within a biofilm and bacteria found in other niches, such as in a wound where oxygen is limited, grow and divide at a far slower speed than the bacteria found in the test tube in the laboratory. Such bacteria are able to adapt to the slower growth rate, once again by changing their chemistry and gene expression pattern.
A further example of adaptation is the phenomenon of chemotaxis, whereby a bacterium can sense the chemical composition of the environment and either moves toward an attractive compound, or shifts direction and moves away from a compound sensed as being detrimental. Chemotaxis is controlled by more than 40 genes that code for the production of components of the flagella that propels the bacterium along, for sensory receptor proteins in the membrane, and for components that are involved in signaling a bacterium to move toward or away from a compound. The adaptation involved in the chemotactic response must have a memory component, because the concentration of a compound at one moment in time must be compared to the concentration a few moments later.
Capsule— A viscous, gelatinous polymer composed either of polysaccharide, polypeptide, or both, that surrounds the surface of some bacteria cells. Capsules increase the disease-causing ability (virulence) of bacteria by inhibiting immune system cells called phagocytes from engulfing them.
Death phase— Stage of bacterial growth when the rate of cell deaths exceeds the number of new cells formed and the population equilibrium shifts to a net reduction in numbers. The population may diminish until only a few cells remain, or the population may die out entirely.
Exotoxins— Toxic proteins produced during bacterial growth and metabolism and released into the environment.
Fimbriae— Short, hairlike, proteinaceous projections that may arise at the ends of the bacterial cell or over the entire surface. These projections let the bacteria adhere to surfaces.
Gram staining— A method for classifying bacteria, developed in 1884 by Danish scientist Christian Gram, which is based upon a bacterium’s ability or inability to retain a purple dye.
Koch’s postulates— A series of laboratory procedures, developed by German physician Robert Koch in the late nineteenth century, for proving that a specific organism cause a specific disease.
Lag phase— Stage of bacterial growth in which metabolic activity occurs but no growth.
Log phase— Stage of bacterial growth when metabolic activity is most intense and cell reproduction exceeds cell death. Also known as exponential phase.
Phage typing— A method for identifying bacteria according to their response to bacteriophages, which are viruses that infect specific bacteria.
Pili— Proteinaceous projections that occur singly or in pairs and join pairs of bacteria together, facilitating transfer of DNA between them.
Spirochetes— Spiral-shaped bacteria which live in contaminated water, sewage, soil and decaying organic matter, as well as inside humans and animals.
Stationary phase— Stage of bacterial growth in which the growth rate slows and the production of new cells equals the rate of cell death.
Life on Earth can be divided into three large collections, or domains. These are the Eubacteria (or “true” bacteria), Eukaryota (the domain that humans belong to), and Archae. The members of this last domain are the archaebacteria.
Most archaebacteria (also called archae) look bacteria-like when viewed under the microscope. They have features that are quite different, however, from both bacteria and eukaryotic organisms. These differences led American microbiologist Carl Woese to propose in the 1970s that archaebacteria be classified in a separate domain of life. Indeed, because the organisms are truly separate from bacteria, Woese proposed that the designation archaebacteria be replaced by archae.
Archae are similar to eukaryotic organisms in that they lack a part of the cell wall called the peptidoglycan. Also, archae and eukaryotes share similarities in the way that they make new copies of their genetic material. However, archae are similar to bacteria in that their genetic material is not confined within a membrane, but instead is spread throughout the cell. Thus, archae represent a blend of bacteria and eukaryotes (some scientists call them the “missing link”), although generally they are more like eukaryotes than bacteria.
Archaebacteria are described as being obligate anaerobes; that is, they can only live in areas without oxygen. Their oxygen-free environments, and the observations that habitats of Archaebacteria can frequently be harsh (so harsh that bacteria and eukaryotic organisms such as humans cannot survive), supports the view that Archaebacteria were one of the first life forms to evolve on Earth.
Archaebacteria are microscopic organisms with diameters ranging from 0.0002–0.0004 in (0.5–1.0 micrometer). The volume of their cells is only around one-thousandth that of a typical eukaryotic cell. They come in a variety of shapes, which can be characterized into three common forms. Spherical cells are called cocci, rod-shaped cells are called bacilli, and spiral cells can either be vibrio (a short helix), spirillum (a long helix), or spirochete (a long, flexible helix). Archaebacteria, like all prokaryotes, have no membrane-bound organelles. This means that the archaebacteria are without nuclei, mitochondria, endoplasmic reticula, lysosomes, Golgi complexes, or chloroplasts. The cells contain a thick cytoplasm that contains all of the molecules and compounds of metabolism and nutrition. Archaebacteria have a cell wall that contains no peptidoglycan. This rigid cell wall supports the cell, allowing an archaebacterium to maintain its shape and protecting the cell from bursting when in a hypo-tonic environment. Because these organisms have no nucleus, the genetic material floats freely in the cytoplasm. The DNA consists of a single circular molecule. This molecule is tightly wound and compact, and if stretched out would be more than 1,000 times longer than the actual cell. Little or no protein is associated with the DNA. Plasmids may be present in the arch-aebacterial cell. These are small, circular pieces of DNA that can duplicate independent of the larger, genomic DNA circle. Plasmids often code for particular enzymes or for antibiotic resistance.
Groups of Archaebacteria
Archaebacteria can be divided into three groups. The first group is comprised of the methane producers (or methanogens). These archaebacteria live in environments without oxygen. Methanogens are widely distributed in nature. Habitats include swamps, deep-sea waters, sewage treatment facilities, and even in the stomachs of cows. Methanogens obtain their energy from the use of carbon dioxide and hydrogen gas.
The second group of Archaebacteria are known as the extreme halophiles. Halophile means “salt loving.” Members of this second group live in areas with high salt concentrations, such as the Dead Sea or the Great Salt Lake in Utah. In fact, some of the archaebacteria cannot tolerate a relatively unsalty environment such as seawater. Halophilic microbes produce a purple pigment called bacteriorhodopsin, which allows them to use sunlight as a source of photosynthetic energy, similar to plants.
The last group of archaebacteria lives in hot, acidic waters such as those found in sulfur springs or deep-sea thermal vents. These organisms are called the extreme thermophiles. Thermophilic means “heat
Chloroplast— Green organelle in higher plants and algae in which photosynthesis occurs.
Domain— One of the three primary divisions of all living systems: Archae, Bacteria, or Eukaryota.
Enzyme— Biological molecule, usually a protein, which promotes a biochemical reaction but is not consumed by the reaction.
Eukaryote— A cell whose genetic material is carried on chromosomes inside a nucleus encased in a membrane. Eukaryotic cells also have organelles that perform specific metabolic tasks and are supported by a cytoskeleton which runs through the cytoplasm, giving the cell form and shape.
Golgi complex— Organelle in which newly synthesized polypeptide chains and lipids are modified and packaged.
Lysosome— The main organelle of digestion, with enzymes that can break down food into nutrients.
Mitochondria— An organelle that specializes in ATP formation, the “powerhouse” of the cell.
Nucleus— A membrane-bound organelle in a eukaryote that isolates and organizes the DNA.
Organelle— An internal, membrane-bound sac or compartment that has a specific, specialized metabolic function.
loving.” They thrive at temperatures of 160°F (70°C) or higher and at pH levels of pH = 1or pH = 2 (the same pH as concentrated sulfuric acid).
Archaebacteria reproduce asexually by a process called binary fission. In binary fission, the bacterial DNA replicates and the cell wall pinches off in the center of the cell. This divides the organism into two new cells, each with a copy of the circular DNA. This is a quick process, with some species dividing once every twenty minutes. Sexual reproduction is absent in the archaebacteria, although genetic material can be exchanged between cells by three different processes. In transformation, DNA fragments that have been released by one bacterium are taken up by another bacterium. In transduction, a bacterial phage (a virus that infects bacterial cells) transfers genetic material from one organism to another. In conjugation, two bacteria come together and exchange genetic material. These mechanisms give rise to genetic recombination, allowing for the continued evolution of the archaebacteria.
Archaebacteria are fundamentally important to the study of evolution and how life first appeared on Earth. The organisms are also proving to be useful and commercially important. For example, methanogens are used to dissolve components of sewage. The methane they give off can be harnessed as a source of power and fuel. Archaebacteria are also used to clean up environmental spills, particularly in harsher environments where most bacteria will fail to survive.
A thermophilic archaebacterium called Thermus aquaticus has revolutionized molecular biology and the biotechnology industry. This is because the cells contain an enzyme that both operates at a high temperature and is key to making genetic material. This enzyme has been harnessed as the basis for a technique called the polymerase chain reaction (PCR). PCR is now one of the bedrocks of molecular biology.
Another increasingly popular reason to study archaebacteria is that they may represent one of the earliest forms of life that existed on earth. This has prompted the suggestion the development of life on other planets may involve similar microbes.