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Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
Antimicrobial peptide resistance in Neisseria meningitidis
Yih-Ling Tzeng1, David S Stephens2
1Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
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.
Insights
Neisseria meningitidis resists antimicrobial peptides (AMPs) through lipid A modification and efflux pumps. These mechanisms provide high intrinsic resistance, crucial for survival in the human respiratory tract.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Antimicrobial peptides (AMPs) are vital for innate immunity against pathogens.
- Neisseria meningitidis, a common nasopharyngeal commensal, causes meningitis and sepsis.
- Meningococci in the respiratory tract encounter host AMPs, necessitating resistance.
Purpose of the Study:
- To review current knowledge on AMP resistance mechanisms in Neisseria meningitidis.
- To highlight the specific molecular strategies meningococci use to evade AMPs.
Main Methods:
- Literature review of studies on Neisseria meningitidis and AMP resistance.
- Analysis of identified resistance mechanisms, including genetic and biochemical factors.
Main Results:
- Neisseria meningitidis employs constitutive lipid A modification and active efflux pumps as major AMP resistance strategies.
- Factors like PorB, pilin apparatus, and capsular polysaccharides also influence AMP resistance.
- Some AMP resistance determinants are inducible upon AMP exposure.
- N. meningitidis lacks several common AMP resistance mechanisms found in other Gram-negative bacteria.
Conclusions:
- Neisseria meningitidis possesses a limited yet highly effective set of molecular mechanisms for AMP resistance.
- Understanding these mechanisms is crucial for combating meningococcal infections.
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