title: Antimicrobial peptide resistance in Neisseria meningitidis.
abstract: Antimicrobial peptides (AMPs) play an important role as a host defense against microbial pathogens and are key components of the human innate immune response. Neisseria meningitidis frequently colonizes the human nasopharynx as a commensal but also is a worldwide cause of epidemic meningitis and rapidly fatal sepsis. In the human respiratory tract, the only known reservoir of N. meningitidis, meningococci are exposed to human endogenous AMPs. Thus, it is not surprising that meningococci have evolved effective mechanisms to confer intrinsic and high levels of resistance to the action of AMPs. This article reviews the current knowledge about AMP resistance mechanisms employed by N. meningitidis. Two major resistance mechanisms employed by meningococci are the constitutive modification of the lipid A head groups of lipooligosaccharides by phosphoethanolamine and the active efflux pump mediated excretion of AMPs. Other factors influencing AMP resistance, such as the major porin PorB, the pilin biogenesis apparatus, and capsular polysaccharides, have also been identified. Even with an inherently high intrinsic resistance, several AMP resistance determinants can be further induced upon exposure to AMPs. Many well-characterized AMP resistance mechanisms in other Gram-negative bacteria are not found in meningococci. Thus, N. meningitidis utilizes a limited but highly effective set of molecular mechanisms to mediate antimicrobial peptide resistance. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides.
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Yih-Ling
authors.initials: YL
authors.lastname: Tzeng
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; Laboratories of Microbial Pathogenesis, Medical Research Service, Veterans Affairs Medical Center, Decatur, GA 30033, USA. Electronic address: dstep01@emory.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Stephens
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D008050:Lipid A / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000517:prevention & control; D050296:Microbial Viability; D009345:Neisseria meningitidis / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D015398:Signal Transduction
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D008050:Lipid A; D026901:Membrane Transport Proteins
keywords: Antimicrobial resistance; Efflux pump; Neisseria meningitidis; Phosphoethanolamine modification of lipid A