How do bacteria rally the troops? Quorum sensing unites them with a verbose chemical language.

There are many languages spoken that humans are just beginning to understand. The speakers of these languages are thousands of bacteria that use tiny molecules to communicate with their brothers and their competition. Alone, a tiny bacterium can inflict little damage on its host and make little change on its environment, but with a coordinated effort they can have huge effects on their surroundings. In years past, scientists believed the simplicity of bacteria meant that they could only act randomly, with little control, but in more recent times it has become clear that microbial communication known as quorum sensing is a complicated, highly controlled process originating from early evolution.

Quorum sensing was first discovered in Vibrio fischeri, a bacterium that exists in a mutual, or symbiotic, relationship with the Hawaiian Bobtail Squid. This particular bacterium creates a luminescent compound, which the squid uses to hunt at night by hosting the bacterial colony in a specialized organ. What scientists found unusual about this relationship is that the bacteria somehow knew when to light up, just in time for the nightly hunting sessions. What they discovered was that the squid released most of the bacteria each day to allow the colony to grow anew while it slept. The bacteria only glowed when enough of them were present and by nightfall, they made light.

That is when researcher Dr. Bonnie Bassler realized they were on to something interesting. She and her team have carried this work to where it is today. Now it is known that the bacteria use small chemical compounds to notify neighbors that they exist. The system of specific chemicals to specific receptors acts like a lock and key. These types of signals are used by many types of bacteria, including those that hurt humans. Dangerous bacteria use these signals to form a coordinated attack only when enough bacteria are present that our body cannot easily destroy them.

In an April 22, 2011 publication of Molecular Cell, Bassler and collaborators altered forms of the small signaling molecule, known as an autoinducer to see how small changes affected the ability of the receptor to receive the chemical message. They found that molecules with small changes, such as having a longer tail or different chemical group at the head of the molecule, fail to create the stability needed for proper interaction with the receptor. In turn this prevents the receptor from binding DNA and making virulence factors. The researchers then reversed their thinking and created mutations on the receptor to alter binding of the autoinducer. Again, disruption of this interaction prevented the message from reaching the DNA.

In more recent work published in Bioorganic and Medicinal Chemistry, Bassler and collaborators looked at the bacteria that cause cholera. In this case, high numbers of bacteria actually turn off virulence factor creation and cause the bacteria to leave the host in unison. This exodus is responsible for the deadly symptoms of diarrhea and dehydration that make cholera such a horrible illness for humans. By creating a library of analogous small molecules to the autoinducer specific to this bacterium, the team was able to look at which structures increased or decreased the signaling potential. They were then able to map exactly which sites on the receptor were essential.

Manipulating this line of communication could improve the way we treat infection. Currently we treat bacterial infections with general antibiotics. These often work by disrupting essential functions for bacterial survival, interfering with the cell’s ability to make a solid cell wall or reproduce for instance. These antibiotics force a great amount of evolutionary pressure on the bacteria, causing the bacteria to invent ways to get around that for survival. This creates antibiotic resistance. By using a more targeted approach that prevents the bacteria from communicating, scientists could create more focused and gentle methods to treat infection without leading to resistance. Now they are speaking my language.

Ref:
 1. Megan E. Bolitho, Lark J. Perez, Matthew J. Koch, Wai-Leung Ng, Bonnie L. Bassler, Martin F. Semmelhack, Small molecule probes of the receptor binding site in the Vibrio cholerae CAI-1 quorum sensing circuit, Bioorganic & Medicinal Chemistry, Volume 19, Issue 22, 15 November 2011, Pages 6906-6918, ISSN 0968-0896, 10.1016/j.bmc.2011.09.021.

2. Guozhou Chen, Lee R. Swem, Danielle L. Swem, Devin L. Stauff, Colleen T. O'Loughlin, Philip D. Jeffrey, Bonnie L. Bassler, Frederick M. Hughson, A Strategy for Antagonizing Quorum Sensing, Molecular Cell, Volume 42, Issue 2, 22 April 2011, Pages 199-209, ISSN 1097-2765, 10.1016/j.molcel.2011.04.003.