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Science. Communication. Community.

Molecular Thermometers Tell Meningococcal Bacteria When To Get Mean

New work by a group of British researchers has found that for one of the species of bacteria that causes meningitis, a trio of exquisitely sensitive RNA thermosensors is behind its shift from harmless commensal to deadly pathogen.

by Jessica McDonald

meningitis

Neisseria meningitidis isolated from a patient. The species of bacteria can cause meningitis, including those this year at Princeton. (Credit: Flickr/Nathan Reading)

Meningitis is not fun. Just ask the eight Princeton students who have come down with a form of the disease caused by the bacterial species Neisseria meningitidis. A highly dangerous inflammation of the namesake membranes surrounding the brain and spinal cord (meninges), bacterial meningitis starts with a headache and stiff neck but can rapidly progress to an uncontrollable, life-threatening infection.

Dr. Jekyll and Mr. Hyde: When Commensals Go Bad

As devastating as N. meningitidis can be when it gets into the meninges or bloodstream, most of the time it’s a commensal—completely innocuous, and happy to live in the deep recesses of human nasal passages. In fact, the WHO estimates that 10-20% of people offer the bacteria safe harbor, nearly all without ill effect. From the perspective of the bacteria, this is a pretty good deal. So it’s puzzling that such a seemingly normal, highly dependent commensal would also have developed the ability to kill off its only food source.

Curious about this paradox, several scientists in the UK began investigating how N. meningitidis is able to evade the human immune system and become pathogenic. Published in the journal Nature this October, the researchers identified three key genes that are responsible for the bacteria’s ability to escape the immune killing, including one that ultimately augments N. meningitidis’s protective capsule (cssA), and another that prevents the innate immune system’s potent complement system from working (fHbp).

Turning Up the Heat

Most remarkably, these strategies are triggered by an increase in temperature, which is detected and controlled by the RNA molecules produced from these three genes. Known as thermosensors, these mRNAs fold back on themselves and create hairpin structures. When the temperature is low, the hairpin is tight, and the ribosome is blocked from coming in and making protein. As the temperature increases, however, the hairpin becomes looser and the ribosome has more access, allowing N. meningitidis to crank out protein and morph into Mr. Hyde, impervious to complement and shielded with plenty of capsule.

RNA thermosensors have been found before in other species of bacteria, including those responsible for bubonic plague (Yersinia pestis) and listerosis (Listeria monocytogenes). In these cases, the increase in temperature is fairly large, with virulence factors turning on only when the bacteria can be confident they have successfully entered a warm body. Interestingly, the thermosensors for N. meningitidis are less like switches, and more like a rheostat that can respond a bit more gradually to a smaller change in temperature—like the added heat of a fever. Indeed, the British researchers suspect that N. meningitidis’s thermosensors are usually inadvertently activated when a person gets infected with something else, such as a virus, noting that meningitis cases tend to spike after influenza outbreaks. Threatened by feverish conditions, the meningococcal bacteria take action to survive, but these same tactics unfortunately make them much better at sticking around in the blood or meninges. In the end, the transformation of the normally harmless N. meningitidis into a scourge of college campuses is really just collateral damage.

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This entry was posted on December 13, 2013 by in Health and tagged , , , , .
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