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Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus.
Shelton, Catherine L; Raffel, Forrest K; Beatty, Wandy L; Johnson, Sara M; Mason, Kevin M.
Afiliação
  • Shelton CL; The Research Institute at Nationwide Children's Hospital, Center for Microbial Pathogenesis, Columbus, Ohio, United States of America.
PLoS Pathog ; 7(11): e1002360, 2011 Nov.
Article em En | MEDLINE | ID: mdl-22072973
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Haemophilus influenzae / Transportadores de Cassetes de Ligação de ATP / Peptídeos Catiônicos Antimicrobianos / Infecções por Haemophilus Limite: Animals Idioma: En Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Haemophilus influenzae / Transportadores de Cassetes de Ligação de ATP / Peptídeos Catiônicos Antimicrobianos / Infecções por Haemophilus Limite: Animals Idioma: En Ano de publicação: 2011 Tipo de documento: Article