Neisseria meningitidis vascular infections: Adaptation and metabolic requirements

• Applicant: Dr. Anna Both
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 469972649

Neisseria meningitidis is a commensal of the human nasopharynx, which is able to cause devastating sepsis and meningitis. In recent years it has become clear that accessing host nutrients during the change in niche (i.e. tissue or bloodstream) is a decisive step in the pathogenesis of most bacterial infections and the term “nutritional virulence” for bacterial strategies dedicated to host nutrient acquisition has been coined. Previous in vitro studies show that N. meningitidis employs different transcriptional and metabolic profiles depending on the experimental setting such as culture on epithelial cells or human whole blood. Some differentially expressed factors related to immune evasion in the bloodstream and attachment to endothelium, such as the polysaccharide capsule and factor H binding proteins have been well described. In addition, metabolic pathways ensuring acquisition of iron have shown significant upregulation in human whole blood. However, infection adaptation of major metabolic pathways still remains to be investigated. This is of particular importance as the bacterial metabolism obviously has direct implications for growth and thus the bacterial load the host has to face, as well as the activity of antibiotics. In this project, we will aim to elucidate metabolic adaptation and requirements of N. meningitidis organized in endothelium attached microcolonies, a pivotal step during infection establishment. To this end, genomic approaches will be combined with high resolution analysis of key metrics such as cell division, protein turnover and cellular ATP- and O2-content in a refined 3D vasculature on a chip model with the ultimate goal to identify new therapeutic targets in meningococcal invasive disease.

• DFG Programme: WBP Fellowship
• International Connection: France
• Host: Dr. Guillaume Duménil