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Understanding how bacteria communicate may help scientists prevent disease

Rahul Kulkarni, assistant professor of physics at Virginia Tech, has been awarded a Ralph E. Powe Junior Faculty Enhancement Award from Oak Ridge Associated Universities to continue his research on quorum sensing in bacteria. He is modeling the sequence of events that initiate activity, such as virulence, by a bacteria colony once it has reached a critical size.

The Powe award provides seed money of $5,000 to faculty members who are in the first two years of their tenure track as an investment in promising achievements in an important area. The institution matches the award.

Much like a legislative body, some bacteria need a quorum, the presence of a critical number of individuals, before they can engage in particular activities. Typically these are activities that are only productive when carried out in unison by a community of bacteria.

The example often given is bioluminescence. Scientists noticed that once a population or colony of particular bacteria reached a certain size, the colony began to emit light. "Now many people realize that other important activities also depend upon a quorum, such as biofilm formation, releasing toxins, or becoming a virulent invader," said Rahul Kulkarni. While Kulkarni works with Vibrio cholerae as a model bacteria, quorum sensing appears to be a universal process in bacteria. So what he learns about the communication process known as quorum sensing could one day help scientists prevent a broad range of diseases caused by bacteria that are human pathogens.

How do bacteria know how many are present? Each bacterium releases a small molecule, called an autoinducer. Each bacterium also has receptors ?proteins on its cell surface -- to sense autoinducers. As the amount of autoinducer reaches a critical level, the bacteria know they have a quorum because a change is initiated in the receptor protein, which then causes a series of further changes within each bacterium.

Kulkarni is looking at the net work of genes involved in this process. Working with a group at Princeton University and at Virginia Tech, "we are trying to understand how changes in the environment are integrated and result in changes in behavior," he said.

What was not known until recently is a crucial missing link in the network in each bacterium that results in the ability to change behavior. Just before he came to Virginia Tech in August 2004, Kulkarni and his collaborators at Princeton solved the mystery. Using bioinformatics and modeling, Kulkarni drafted theoretical predictions for the missing regulatory element, which were confirmed experimentally by his colleagues at Princeton.

"We showed that the crucial missing element was a group of genes called small RNAs. ("The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae," by D.H. Lenz, K.C. Mok, B.N. Lilley, R.V. Kulkarni, N.S. Wingreen, and B.L. Bassler, published in Cell, July 9, 2004). "As it turns out, quorum sensing is a hot topic in biology, and small RNAs is another hot topic. The convergence of these topics is exciting, and it has resulted in several additional questions," Kulkarni said.

He will address these questions in his Powe-funded research. "We are asking, what are the environmental signals, apart from quorum sensing, that are integrated by the small RNAs to initiate changes in behavior. An example might be the amount of nutrients in the environment. Another question is why are there multiple RNAs? The sensing and communication circuit functions even if some of the RNAs are removed ?in fact, even if there is only one small RNA. Modeling the circuit will be crucial in understanding how it functions and integrates signals from multiple inputs," Kulkarni said.

A third question is how the circuit regulates important biological processes, such as biofilm formation and virulence. "Biofilms make bacteria resistant to antibiotics, so preventing t he formation of biofilms or short-circuiting bacteria's ability to become virulent by disturbing their communication network so they remain harmless, is an alternative strategy to controlling disease," he said.

Kulkarni will continue his collaboration with the Princeton University group on V. cholerae and will collaborate with Virginia Tech Biology Professor Ann Stevens, whose group is working on V. fischeri, the bacteria that causes luminescence and whose genome has recently been sequenced ("Complete genome sequence of Vibrio fischeri: A symbiotic bacterium with pathogenic congeners," by E. G. Ruby, M. Urbanowski, J. Campbell, A. Dunn, M. Faini, R. Gunsalus, P. Lostroh, C. Lupp, J. McCann, D. Millikan, A. Schaefer, E. Stabb, A. Stevens, K. Visick, C. Whistler, and E. P. Greenberg, published Feb. 22, 2005 in the Proceedings of the National Academy of Science.).

Kulkarni received his Master of Science degree in physics from the Indian Institute of Technology in Kanpur and his Ph.D. in physics from Ohio State University. He was a postdoctoral researcher at the University of California, Davis, and a postdoctoral research scientist at the NEC Laboratories America Inc. in Princeton, N.J.


Source:Virginia Tech

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