Meningitis pathogens evade immune responses by thermosensing

Bacterial meningitis is a major cause of death and disability in children worldwide. Two human restricted pathogens, Streptococcus pneumoniae and Haemophilus influenzae are the major causative agents of bacterial meningitis, attributing to 200,000 deaths annually. These pathogens are often part of the nasopharyngeal microflora of healthy carriers. However, what factors elicit them to disseminate and cause invasive diseases remain unknown. Elevated temperature and fever are hallmarks of inflammation triggered by infections and can act as warning signal to these pathogens. Here, we investigate whether these pathogens could sense environmental temperature to evade host complement mediated killing. We show that expression of two vital virulence factors and vaccine components, the capsule and factor H binding proteins, are temperature dependent. We identify and characterize four novel RNA thermosensors in S. pneumoniae and H. influenzae within their 5-Prime-untranslated regions of genes responsible for capsular biosynthesis and production of factor H binding proteins. Our data further demonstrate that these pathogens have co-evolved thermosensing abilities independently with unique RNA sequences, but distinctive secondary structures to evade the human immune system.