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Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus

Catherine L Shelton1, Forrest K Raffel, Wandy L Beatty

  • 1The Research Institute at Nationwide Children's Hospital, Center for Microbial Pathogenesis, Columbus, Ohio, United States of America.

Plos Pathogens
|November 11, 2011
PubMed

Insights

Nontypeable Haemophilus influenzae uses the Sap transporter to import antimicrobial peptides (AMPs) into the cytoplasm, neutralizing their infection-fighting effects. This mechanism protects bacteria from host defense peptides.

Area of Science:

  • Microbiology
  • Immunology
  • Biochemistry

Background:

  • Antimicrobial peptides (AMPs) are crucial for innate immunity against bacterial infections.
  • Nontypeable Haemophilus influenzae (NTHI) causes opportunistic respiratory infections and resists AMPs.
  • The Sap ABC transporter in NTHI is known to confer resistance to AMPs, but the mechanism is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which the Sap transporter mediates NTHI resistance to antimicrobial peptides.
  • To investigate the role of SapA in the interaction with and resistance to AMPs during infection.

Main Methods:

  • Antibody-mediated neutralization of AMPs in vivo.
  • Localization studies of AMPs in NTHI strains (parental and Sap permease deficient).
  • Assessment of AMP susceptibility to cytoplasmic peptidase activity.

Main Results:

  • SapA was confirmed to directly counteract AMP lethality in vivo.
  • Antimicrobial peptides were found to localize to the bacterial cytoplasm in wild-type NTHI.
  • AMPs accumulated in the periplasm of NTHI lacking a functional Sap permease complex, indicating impaired import.
  • Cytoplasmic localization rendered AMPs susceptible to degradation.

Conclusions:

  • The Sap ABC transporter facilitates the import of antimicrobial peptides into the NTHI cytoplasm.
  • This import mechanism represents a novel bacterial strategy to evade host innate immunity by neutralizing AMPs.
  • Sap-mediated AMP import reduces the accumulation of these host defense peptides in the periplasm and at the inner membrane.

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