Chapter 14, Problem 6CHI

Neisseria meningitidis, commonly called meningococcus, causes meningitis, a serious infection of the membranes surrounding the brain and spinal cord (meninges); these infections often lead to death. Surprisingly, meningococcus is a normal inhabitant of the nasopharynx in about a third of humans, where it causes no harm. It was known that meningococcal meningitis often follows an inflammatory response such as one caused by influenza. Inflammatory responses are often accompanied by an increase in temperature, especially in the tissues where the response occurs. Thus, in the case of influenza, inflammation of the nasopharynx would expose the meningococcus bacteria to higher temperatures and contribute to the development of meningitis. Knowing this, scientists wondered how the bacterium sensed the temperature increase and how this contributed to its ability to escape human defenses, cross the blood-brain barrier, and cause disease. Scientists in the United Kingdom tried to answer this question by isolating mutants resistant to immune system defenses present in human serum when exposed to the serum at body temperature. They then characterized the mutated genes and found that each had a small change in the 5′ untranslated region (5' UTR) that altered its response to temperature. The normal, wild-type gene was expressed at high levels only when the bacterium was exposed to higher temperatures, whereas the mutant genes were expressed at high levels even when the bacteria were exposed to lower temperatures (e.g., body temperature). Thus the 5′ UTR was involved in regulating expression of these genes in response to temperature, and the scientists referred to it as a thermosensor. One of the genes (cssA) encodes an enzyme involved in capsule formation, and its higher expression leads to bacteria forming more capsular material, thus rendering them resistant to a variety of host defenses. Suggest a mechanism by which the 5′ UTR might function as a thermosensor. (HINT: Remember that the 5′ UTR is transcribed into mRNA but is not translated.)

Read the original paper: Loh, E., et al. 2013. Temperature triggers immune evasion by Neisseria meningitidis. Nature 502:237.