Characterization of Neisseria meningitidis GNA2132 antigen, a heparin binding protein cleaved by meningococcal NalP protease

ABSTRACT GNA2132 (Genome-derived Neisseria Antigen 2132), a protein discovered by Reverse Vaccinology, is a surface-exposed lipoprotein expressed by genetically diverse Neisseria meningitidis strains. The protein induces bactericidal antibodies against most strains of meningococccus and has been included in a multivalent recombinant vaccine against N. meningitidis serogroup B. Sequence analysis of GNA2132 revealed the presence of an Arginine-rich region highly conserved among different strains. In this study we described that in meningococcus the protein is cleaved upstream from the Arginine-rich region and the C-terminal fragment is released in the culture supernatant. By genetic approaches we demonstrated that the processing of GNA2132 is strain-dependent and correlates with the expression of NalP, a phase variable autotransporter with a serine-protease activity, which has been previously shown to cleave known Neisseria virulence factors. Sequence analysis of GNA2132 protein revealed the presence of an Arginine-rich region highly conserved among N. meningitidis strains. Our functional studies revealed that this region is crucial for the function of GNA2132 since recombinant GNA2132 binds heparin through the Arginine-rich region motif.