Novel hypercapsulation RNA thermosensor variants in Neisseria meningitidis and their association with invasive meningococcal disease: a genetic and phenotypic investigation and molecular epidemiological study

作者：Jens Karlsson, Hannes Eichner, Cecilia Andersson, Susanne Jacobsson, Edmund Loh · 发表于：The Lancet Microbe · 年份：2020 · DOI：10.1016/s2666-5247(20)30146-4 · 被引用次数：17 · 研究领域：Bacterial Infections and Vaccines、Bacterial Genetics and Biotechnology、Pneumonia and Respiratory Infections

BACKGROUND: Neisseria meningitidis is the causative agent of invasive meningococcal disease and the polysaccharide capsule is one of its major virulence factors. Biosynthesis of the meningococcal capsule is controlled by an RNA thermosensor (RNAT) in the 5'-untranslated region (5'-UTR) of the cssA gene. The function of the RNAT depends on an 8-bp tandem repeat configuration. We aimed to identify and characterise novel RNATs in meningococcal isolates responsible for regulating capsule production. METHODS: We investigated the allele igr_up_NEIS0055, containing the 5'-UTR of the cssA gene, in clinical meningococcal isolates for which whole-genome sequences are available on the Neisseria PubMLST database and that were isolated in Europe between Jan 1, 2010, and Dec 31, 2018. Eight isolates with different RNAT tandem repeat configurations were selected for genetic and phenotypic studies. The thermosensing capability of the RNAT and capsule production was tested with immunoblots. Bacterial survival by capsule protection was assessed with a human serum stress assay and capsule interference with bacterial cell adhesion was evaluated with a bacterial adhesion assay. The dataset of RNAT configurations was analysed for an association with invasive meningococcal disease, and was stratified to visualise the distribution of RNAT configurations within the meningococcal population. FINDINGS: Our search of PubMLST identified 112 alleles for the igr_up_NEIS0055 locus and 7013 N meningitidis is...