Functional characterization of selected meningococcal autotransporter proteins

Neisseria meningitidis is a Gram-negative bacterium which can cause devastating outbreaks of meningitis and septicaemia. Meningococci elaborate numerous cell-surface and secreted virulence factors which facilitate colonization of, persistence in, and damage to, the host. One important class are the autotransporter (or type V secreted) proteins. Eight autotransporter proteins have been identified in meningococci, five of which were first discovered in our laboratory. This project will focus on the autotransporters IgA1 protease; App; MspA and NalP. These are secreted proteases which cleave various bacterial surface and/or host cell proteins, but their exact repertoire of targets and therefore precisely how they contribute to pathogenicity are still unclear. This project will be to investigate host cell receptors, uptake pathways, proteolytic targets, signalling events and phenotypic changes mediated by the autotransporters to provide new insights into pathogenesis. This will provide training in tissue culture, confocal microbiology, flow cytometry, protein biochemistry and molecular microbiology.