Bacteria can 1) ___ between species, and have evolved mechanisms to interfere with the communication. Probably this is but one of many cunning strategies bacteria have for manipulating chemical communication. Certain snippets of their chemical conversation are almost universally understood. Howard Hughes Medical Institute researchers have found that bacteria of different 2) ___ can talk to each other using a common language, and that some species can manipulate the conversation to confuse other bacteria. The interspecies crosstalk and misdirection could have important consequences for 3) ___ health. The ability of cells to communicate with one another and the ability to interfere with the communication process could have consequences in niches containing competing species of bacteria or in niches where bacteria associate with humans. In the gut, the normal 4) ___ might interfere with cell-cell communication to thwart bacterial invaders. Using a chemical communication process called 5) ___ ___, bacteria converse among themselves to count their numbers and to get the population to act in unison. A synchronized group of bacteria can mimic the power of a multi-cellular 6) ___, ready to face challenges too daunting for an individual microbe going it alone. Swelling populations trigger their quorum-sensing apparatuses, which have different effects in different types of bacteria. One species might respond by releasing a 7) ___, while another might cut loose from a biofilm and move on to another environment. Each species of bacteria has a private 8) ___, but most also share a molecular vernacular, discovered about 10 years ago. A chemical signal called autoinducer-2 (AI-2), originating from the same gene in all bacteria, is released outside the cell to announce the cell’s 9) ___. Nearby bacteria take a local census by monitoring AI-2 levels and conduct themselves as the circumstances warrant. Researchers have speculated that AI-2 is a universal language, and the new studies from Princeton are the first to show those conversations taking place – and producing consequences — between co-mingling species. But this common language does not guarantee that the correct 10) ___ gets through. In an earlier study, it was found, that E. coli both produce and consume AI-2. This study set up an experiment where multitudes of E. coli first produced then devoured enough AI-2 to confuse marine bacteria, essentially fooling the thriving oceanic group into thinking its members were few, thereby terminating its quorum-sensing behaviors. In a more realistic encounter, E. coli was mixed with V. cholerae , the cholera-causing bacteria that mixes with E. coli in human guts. When cholera bacteria sense a quorum, they turn off their toxins and excrete an enzyme to cut themselves loose from the intestine in order move out of the body where they can infect another person. Here, E. coli squelched much of the quorum-sensing response of the cholera bacteria, although the effect was not as dramatic as with the marine bacteria. Consumption of the signal could be a mechanism that allows one kind of bacteria to block another kind of bacteria from counting how many neighbors they have and, in turn, properly controlling its behavior. This study moves us closer to really understanding how these 11) ___ interactions happen in nature.

ANSWERS: 1) communicate; 2) species; 3) human; 4) microflora; 5) quorum sensing; 6) organism; 7) toxin; 8) language; 9) presence; 10) message; 11) chemical

This past week, Dr. Glen Park, Sr. Director, Clinical and Regulatory Affairs presided at a very successful, highly interactive Pre-CTA meeting in Ottawa. The weather was beautiful and the view of the Ottawa River from the meeting room was breathtaking. The project is already ongoing in Israel, South Africa, and the US and will be shortly starting in Europe. Target Health is monitoring in the US and Canada, and performing 1) the global EDC trial, 2) data management, 3) biostatistics and 4) medical writing. We will also submit the NDA at the completion of the program.

For more information, please contact Dr. Jules T. Mitchel or Joyce Hays. For new business opportunities, contact Adrian Pencak, (Vice President, Business Development).