No abstract

Bacterial pathogens face stringent challenges to their survival because of the many unpredictable, often precipitate, and dynamic changes that occur in the host environment or in the process of transmission from one host to another. Bacterial adaptation to their hosts involves either a mechanism for sensing and responding to external changes or the selection of variants that arise through mutation. Here we review how bacterial pathogens exploit localized hypermutation, through polymerase slippage of simple sequence repeats (SSRs), to generate phenotypic variation and enhanced fitness. These SSRs are located within the reading frame or in the promoter of a subset of genes, often termed contingency loci, whose functions are usually involved in direct interactions with host structures.

GNA2132 is a Neisseria meningitidis antigen of unknown function, discovered by reverse vaccinology, which has been shown to induce bactericidal antibodies in animal models. Here we show that this antigen induces protective immunity in humans and it is recognized by sera of patients after meningococcal disease. The protein binds heparin in vitro through an Arg-rich region and this property correlates with increased survival of the unencapsulated bacterium in human serum. Furthermore, two proteases, the meningococcal NalP and human lactoferrin, cleave the protein upstream and downstream from the Arg-rich region, respectively. We conclude that GNA2132 is an important protective antigen of N. meningitidis and we propose to rename it, N eisserial H eparin B inding A ntigen (NHBA).