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In recently published  into the regulatory mechanisms of a disease bacterium often found in the human body, ������Ƶ Heritage College of Osteopathic Medicine Associate Professor of Bacteriology Erin Murphy, Ph.D., and her team didn’t find what they went looking for. What they did find, however, opens more research pathways, suggesting science has more to learn about the tools different bacterial pathogens use to adapt to changes in their environment.

Murphy is a member of both the Infectious and Tropical Disease Institute and OHIO’s interdisciplinary Molecular and Cellular Biology Program (MCB). She and her research team – including collaborators from ������Ƶ, Egypt and Germany – were trying to identify a temperature-sensitive mechanism that regulates gene expression in Staphylococcus aureus. This is the well-known bacterium many people carry in their nostrils that sometimes penetrates further into the body, causing harmful infections.

As S. aureus moves from the nose to inside the body, its surroundings get warmer. In some bacteria, such a temperature increase triggers changes in gene expression that may better equip the germ to survive in its new environment – which is bad health news for the human whose body the staph has invaded.

Looking for a genetic thermometer

Temperature-sensing regulators called “RNA thermometers,” found in the structure of the messenger RNA molecule (which transmits genetic information from DNA), have been discovered in other bacteria. For instance, Murphy and her collaborators have identified such a mechanism in the Shigella bacterium.

They set out to find something similar in S. aureus. Instead, they found a mechanism that responds to temperature changes in the opposite way to RNA thermometers previously encountered – instead of increasing expression of a gene as temperature goes up, this mechanism increased expression as temperature drops. The gene in this case controls production of a protein called CidA.

“What we were looking for was a traditional thermometer,” Murphy explained. “Those mediate increased expression of the gene at increased temperature. But here we found decreased expression of our targeted gene. So it’s temperature-regulated, but it’s expressed less at 37 (degrees Celsius) as compared to lower temperatures.” (When staph moves from the nostrils to inside the body, the temperature increases from about 30 degrees to about 37.)

This is only the second such RNA “thermosensor” – one responding to drops rather than rises in temperature – ever found in a bacterial organism, and the first one found in Staphylococcus. This provides a clue that bacterial pathogens have a wider range of adaptive tools than previously realized.

As Murphy and her co-authors put it in a paper published in the journal Plos One : “In addition to the characterization of the first RNA-based thermosensor in the significant pathogen S. aureus, (this finding) highlights the diversity of function within this important class of ribo-regulators.”

Might we turn off S. aureus’ thermostat?

Understanding temperature-responsive regulation of bacterial gene expression raises the possibility that down the line, a drug might be found to lock the thermosensor into its low-temperature setting. If this could be done, it would mean that when S. aureus moved from the nose to warmer places inside the body, the change in temperature would not trigger a change in gene expression, and the bacterium would not benefit from whatever survival advantage that change normally provides.

“This mechanism of regulation is quite amenable to being manipulated,” said Ronan Carroll, Ph.D., OHIO assistant professor of microbio