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GEN News Highlights : Apr 12, 2007

Scientist Determine Structure of Infection-Causing Transcription Factor in Bacteria

RfaH regulates transcription of genes in E. coli that produce infection and protect it from immune systems.

The results of a new study suggest that a particular transcription factor in certain disease-causing bacteria can turn the genes that make them infectious on or off.

Every type of bacteria known contains the transcription factor NusG, which controls nearly all of a bacterium's gene expression. A specialized transcription factor called RfaH directs only a small portion of gene expression. This section turns out to be important, as RfaH turns on those genes that give bacteria like E. coli and Yersinia pestis  their ability to infect.

Researchers at Ohio State University used X-ray techniques to study and describe RfaH proteins extracted from E. coli. They found that while about two-thirds of RfaH's structure closely resembles the structure of NusG, the remaining one-third looked dramatically different. This latter third appears to be the portion of the protein responsible for controlling the genes that make E. coli infectious.

“In contrast to NusG, which is always active, RfaH is usually inactive because the part of the protein that is needed to activate gene expression is typically masked,” explains Vladimir Svetlov, co-author and a research associate in microbiology.

It's only when RfaH finds the appropriate target sequence on a bacterium's DNA that this small portion of the protein is unmasked and can then turn on a select group of genes during transcription. These genes let disease-causing bacteria infect their host while at the same time protect the bacteria from the host's immune defenses.

“Making RfaH work only at specific sites is, in a sense, a genius way to prevent it from interfering with NusG,” remarks Irina Artsimovitch, Ph.D., the study's lead author and an associate professor of microbiology. “It seems that the only genes that RfaH can't regulate are those controlled by NusG.”

The findings appear in the April 13 issue of the journal Molecular Cell.