title: A streptococcal penicillin-binding protein is critical for resisting innate airway defenses in the neonatal lung.
abstract: Group B streptococcus (GBS) is a major cause of neonatal pneumonia. The early interactions between innate airway defenses and this pathogen are likely to be a critical factor in determining the outcome for the host. The surface-localized penicillin-binding protein (PBP)1a, encoded by ponA, is known to be an important virulence trait in a sepsis model of GBS infection that promotes resistance to neutrophil killing and more specifically to neutrophil antimicrobial peptides (AMPs). In this study, we used an aerosolization model to explore the role of PBP1a in evasion of innate immune defenses in the neonatal lung. The ponA mutant strain was cleared more rapidly from the lungs of neonatal rat pups compared with the wild-type strain, which could be linked to a survival defect in the presence of alveolar macrophages (AM). Rat AM were found to secrete beta-defensin and cathelicidin AMP homologues, and the GBS ponA mutant was more susceptible than the wild-type strain to killing by these peptides in vitro. Collectively, our observations suggest that PBP1a-mediated resistance to AM AMPs promotes the survival of GBS in the neonatal lung. Additionally, AM are traditionally thought to clear bacteria through phagocytic uptake; our data indicate that secretion of AMPs may also participate in limiting bacterial replication in the airway.
authors: Division of Infectious Disease, Children's Hospital and Regional Medical Center, and Department of Pediatrics, University of Washington, 307 Westlake Avenue N., Seattle, WA 98109, USA. amanda.jones@seattlechildrens.org
authors: Amanda L
authors: AL
authors: Jones
authors: Robert H
authors: RH
authors: Mertz
authors: David J
authors: DJ
authors: Carl
authors: Craig E
authors: CE
authors: Rubens
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D005260:Female; D007113:Immunity, Innate; D008168:Lung / Q000254:growth & development / Q000276:immunology* / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D046915:Penicillin-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D023083:beta-Defensins / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D023083:beta-Defensins; D054804:Cathelicidins