title: Neisseria meningitidis NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum.
abstract: The complement system is a crucial component of the innate immune response against invading bacterial pathogens. The human pathogen Neisseria meningitidis (Nm) is known to possess several mechanisms to evade the complement system, including binding to complement inhibitors. In this study, we describe an additional mechanism used by Nm to evade the complement system and survive in human blood. Using an isogenic NalP deletion mutant and NalP complementing strains, we show that the autotransporter protease NalP cleaves C3, the central component of the complement cascade. The cleavage occurs 4 aa upstream from the natural C3 cleavage site and produces shorter C3a-like and longer C3b-like fragments. The C3b-like fragment is degraded in the presence of the complement regulators (factors H and I), and this degradation results in lower deposition of C3b on the bacterial surface. We conclude that NalP is an important factor to increase the survival of Nm in human serum.
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Del Tordello
authors.forename: Irene
authors.initials: I
authors.lastname: Vacca
authors.forename: Sanjay
authors.initials: S
authors.lastname: Ram
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Davide
authors.initials: D
authors.lastname: Serruto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003176:Complement C3 / Q000737:chemistry* / Q000276:immunology; D003179:Complement C3b / Q000737:chemistry* / Q000276:immunology; D017242:Complement Factor H / Q000737:chemistry; D017244:Complement Factor I / Q000737:chemistry; D004247:DNA / Q000235:genetics; D004926:Escherichia coli / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000378:metabolism*; D044967:Serum / Q000382:microbiology*; D013045:Species Specificity; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
chemical_list: D003176:Complement C3; D026901:Membrane Transport Proteins; D003179:Complement C3b; D017242:Complement Factor H; D004247:DNA; C480853:NalP protein, Neisseria meningitidis; D012697:Serine Endopeptidases; D017244:Complement Factor I
keywords: immune evasion; serum resistance