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

Antimicrobial peptides (AMPs) contribute to host innate immune defense and are a critical component to control bacterial infection. Nontypeable Haemophilus influenzae (NTHI) is a commensal inhabitant of the human nasopharyngeal mucosa, yet is commonly associated with opportunistic infections of the...

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Autores principales:	Catherine L Shelton, Forrest K Raffel, Wandy L Beatty, Sara M Johnson, Kevin M Mason
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cea38e8d86fe4321b02c8e0a44d1f736
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spelling	oai:doaj.org-article:cea38e8d86fe4321b02c8e0a44d1f7362021-11-18T06:05:09ZSap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus.1553-73661553-737410.1371/journal.ppat.1002360https://doaj.org/article/cea38e8d86fe4321b02c8e0a44d1f7362011-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22072973/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Antimicrobial peptides (AMPs) contribute to host innate immune defense and are a critical component to control bacterial infection. Nontypeable Haemophilus influenzae (NTHI) is a commensal inhabitant of the human nasopharyngeal mucosa, yet is commonly associated with opportunistic infections of the upper and lower respiratory tracts. An important aspect of NTHI virulence is the ability to avert bactericidal effects of host-derived antimicrobial peptides (AMPs). The Sap (sensitivity to antimicrobial peptides) ABC transporter equips NTHI to resist AMPs, although the mechanism of this resistance has remained undefined. We previously determined that the periplasmic binding protein SapA bound AMPs and was required for NTHI virulence in vivo. We now demonstrate, by antibody-mediated neutralization of AMP in vivo, that SapA functions to directly counter AMP lethality during NTHI infection. We hypothesized that SapA would deliver AMPs to the Sap inner membrane complex for transport into the bacterial cytoplasm. We observed that AMPs localize to the bacterial cytoplasm of the parental NTHI strain and were susceptible to cytoplasmic peptidase activity. In striking contrast, AMPs accumulated in the periplasm of bacteria lacking a functional Sap permease complex. These data support a mechanism of Sap mediated import of AMPs, a novel strategy to reduce periplasmic and inner membrane accumulation of these host defense peptides.Catherine L SheltonForrest K RaffelWandy L BeattySara M JohnsonKevin M MasonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 11, p e1002360 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Catherine L Shelton Forrest K Raffel Wandy L Beatty Sara M Johnson Kevin M Mason Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus.
description	Antimicrobial peptides (AMPs) contribute to host innate immune defense and are a critical component to control bacterial infection. Nontypeable Haemophilus influenzae (NTHI) is a commensal inhabitant of the human nasopharyngeal mucosa, yet is commonly associated with opportunistic infections of the upper and lower respiratory tracts. An important aspect of NTHI virulence is the ability to avert bactericidal effects of host-derived antimicrobial peptides (AMPs). The Sap (sensitivity to antimicrobial peptides) ABC transporter equips NTHI to resist AMPs, although the mechanism of this resistance has remained undefined. We previously determined that the periplasmic binding protein SapA bound AMPs and was required for NTHI virulence in vivo. We now demonstrate, by antibody-mediated neutralization of AMP in vivo, that SapA functions to directly counter AMP lethality during NTHI infection. We hypothesized that SapA would deliver AMPs to the Sap inner membrane complex for transport into the bacterial cytoplasm. We observed that AMPs localize to the bacterial cytoplasm of the parental NTHI strain and were susceptible to cytoplasmic peptidase activity. In striking contrast, AMPs accumulated in the periplasm of bacteria lacking a functional Sap permease complex. These data support a mechanism of Sap mediated import of AMPs, a novel strategy to reduce periplasmic and inner membrane accumulation of these host defense peptides.
format	article
author	Catherine L Shelton Forrest K Raffel Wandy L Beatty Sara M Johnson Kevin M Mason
author_facet	Catherine L Shelton Forrest K Raffel Wandy L Beatty Sara M Johnson Kevin M Mason
author_sort	Catherine L Shelton
title	Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus.
title_short	Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus.
title_full	Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus.
title_fullStr	Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus.
title_full_unstemmed	Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus.
title_sort	sap transporter mediated import and subsequent degradation of antimicrobial peptides in haemophilus.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/cea38e8d86fe4321b02c8e0a44d1f736
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Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus.

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