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.

Keywords: Antimicrobial resistance; Efflux pump; Neisseria meningitidis; Phosphoethanolamine modification of lipid A.

Figure 1

A schematic summary of cellular factors influencing antimicrobial peptide resistance in Neisseria meningitidis. AMPs can initiate the self-promoted uptake through electrostatic interactions with negatively charged lipopolysaccharides of the outer membrane or through the secretin apparatus of type IV pili. The constitutive PEA modification of lipid A head groups reduces electrostatic interactions of AMPs with the cell envelop, while both capsule and bleb act to sequester AMPs from reaching the cell surface. The Mtr efflux pump can expel AMPs from either periplasm or cytoplasm by active efflux, and the major outer membrane porin, PorB, also likely functions as an excretion channel.