Just How do Bacteria Communicate?

Chemical engineer develops way to short-circuit biofilm formation

By Seán ottewell, Editor at Large

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Biofilms bring trouble. They account for more than 80% of microbial infections in the body, according to the National Institutes of Health (http://www.nih.gov/), Behesda, Md.

Examples include infections of the oral soft tissues, middle ear, gastrointestinal tract, urinogenital tract, airway/lung tissue, and the eye. Manmade devices suffer similarly, with in-dwelling catheters, pacemakers, prosthetic heart valves, stents and ventilator tubing at risk too.

Biofilm-associated microorganisms tend to be far more resistant to antimicrobial agents and make it particularly difficult for the host immune system to render an appropriate response.

As such, they also may be behind the re-emergence of new forms of well-known disorders. For example, a paper in the June 11 issue of Molecular Microbiology shows that biofilms could be the source of drug-tolerant tuberculosis (TB) strains.

In their paper, two University of Pittsburgh authors show that TB bacteria Mycobacterium tuberculosis can grow in surface-level clusters — biofilms — that are common in nature but which have never been seen before with such bacteria. These biofilm bacteria are both physically and genetically different from TB bacteria harvested in a laboratory — the ones used to develop antibiotics. (You can see the citation here: http://www3.interscience.wiley.com/journal/119878863/abstract?CRETRY=1&SRETRY=0)

These variations result in bacteria that are “drugtolerant and harbor persistent cells that survive high concentrations of anti-tuberculosis antibiotics,” the authors note.

However, understanding how bacterial cells “talk” to each other could lead to more effective methods for fighting persistent and serious infections. Thomas K. Wood, a professor of chemical engineering at Texas A&M University, College Station, Texas, has deciphered their language as well as discovered how to quell their conversation by examining Escherichia coli (E. coli) bacteria.

His findings are covered in a series of five published articles, two of which appear in The International Society for Microbial Ecology Journal and the others in The Public Library of Science ONE (http://www.plos.org), Applied and Environmental Engineering and BMC Microbiology (http://www.biomedcentral.com/bmcmicrobiol/).

Two of Woods' articles

"Indole cell signaling occurs primarily at low temperatures in Escherichia coli" at http://www.nature.com/ismej/journal/vaop/ncurrent/abs/ismej200854a.html 

"Escherichia coli transcription factor YncC (McbR) regulates colanic acid and biofilm formation by repressing expression of periplasmic protein YbiM (McbA)" at http://www.nature.com/ismej/journal/v2/n6/abs/ismej200824a.html

“When bacteria are growing within a biofilm, that growth takes place in a different way than when bacteria are swimming freely in suspension,” says Woods. “Pharmaceutical firms make antibiotics to kill bacteria in suspension. Those are 1,000 times less effective on a biofilm. It’s only in the last 10 years that we’ve realized people have died not because of free-floating bacteria but because of bacteria in a biofilm.”

Wood’s efforts to mitigate biofilm formation began with recognizing that construction of this substance was anything but random. Each bacterial cell can “talk” to its neighbor and signal its location using a compound called autoinducer-2 (AI-2). Once a specific concentration of AI-2 has been reached in the spaces between the bacterial cells, it begins to re-enter them. Only now the compound activates an entirely new set of behaviors — in this case, signaling when and how to begin building a biofilm.

“Sugars are the mortar. We identified the specific type of mortar — the sugar known as colonic acid. We found that AI-2 helps E. coli produce more biofilm by making colonic acid. If you can understand how a biofilm is formed, then you can start to attack it at different stages,” he explains.

Further research by Wood revealed that E. coli uses two different signals to control biofilm formation. Which signal is utilized depends on the temperature of the external environment. In other words, these bacteria change their “language” if they are inside versus outside the body. Whereas AI-2 is the signal utilized by E. coli inside the body, Wood discovered that a compound known as indole is used for biofilm growth outside of the body — for instance on surgical replacement parts yet to be implanted.

“The second signal that we unraveled is indole — a derivative of amino acids,” he says. “Amino acids are what proteins are made out of. All living things need to make amino acids. All living things make this specific amino acid called tryptophan. It turns outs E. coli converts tryptophan into indole.”

“Once we realized that indole was the signal, then we could slightly modify indole by putting a hydroxide molecule on it. The new compound is called 7-hydroxyindole. We also found that a different type of modification would not be successful. We learned that you can trick bacteria, but you have to do it well, and another modification does not have any effect on stopping biofilm formation. By adding that hydroxyl group and making the 7-hydroxyindole, we turn off the bacterium’s ability to talk. We short-circuit the bacterium, and it becomes less of a bad actor,” he concludes.

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