A regulatory RNA is associated to invasive meningococcal disease in Europe

Abstract

The strictly human pathogen Neisseria meningitidis is a commensal bacterium but can occasionally turn lethal causing septicaemia and meningitis. The mechanisms of how the meningococcus shifts to invasive infection remain poorly understood. Here we demonstrate that an eight base-pair tandem repeat deletion in the 5-untranslated region of the polysaccharide capsular biosynthesis operon results in a hypercapsulation phenotype in clinical isolates. The increased capsule production significantly improves the bacterium survival in human serum while impairing its ability to adhere and colonise human pharyngeal cells. Among 4501 reported meningococcal cases in Europe from 2010-2018, the loss of an eight base-pair tandem repeat is three times more prevalent in invasive isolates (16.3%) compared to carrier isolates (5.1%).Combined results indicate that polymorphisms in this regulatory RNA contributes to meningococcal virulence.\n\nImportanceIn this study we report a regulatory RNA to be directly involved in clinical manifestation of meningococcal disease. Using readily accessible WGS of meningococcus, we have now demonstrated that regulatory RNAs directly contribute to the progression of invasive meningococcal infection. We believe this novel combination of molecular and comparative regulatory RNA study could be used for the identification of additional RNAs involved in not only meningococcus but also pave the way for similar studies in other important bacterial pathogens. The identification of specific regulatory RNAs will no doubt facilitate clinicians, microbiologists, and public health practitioners to adjust their diagnostic techniques and treatments to best fit the condition of the patients.