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A streptococcal penicillin-binding protein is critical for resisting innate airway defenses in the neonatal lung

Amanda L Jones1, Robert H Mertz, David J Carl

  • 1Division 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

Journal of Immunology (Baltimore, Md. : 1950)
|August 22, 2007
PubMed

Insights

Group B Streptococcus (GBS) uses penicillin-binding protein 1a (PBP1a) to evade killing by lung immune cells. This protein enhances GBS survival against antimicrobial peptides secreted by alveolar macrophages in neonatal pneumonia.

Area of Science:

  • Neonatal immunology
  • Bacterial pathogenesis
  • Innate immunity

Background:

  • Group B Streptococcus (GBS) is a leading cause of neonatal pneumonia.
  • Early host-pathogen interactions in the neonatal airway are critical for disease outcome.
  • Penicillin-binding protein 1a (PBP1a) is a GBS virulence factor promoting resistance to neutrophil killing.

Purpose of the Study:

  • To investigate the role of PBP1a in GBS evasion of neonatal lung innate immune defenses.
  • To explore PBP1a's contribution to GBS survival against alveolar macrophage antimicrobial peptides.

Main Methods:

  • Utilized an aerosolization model in neonatal rat pups to study GBS infection.
  • Compared the clearance of wild-type GBS and a ponA mutant strain from the lungs.
  • Assessed GBS susceptibility to rat alveolar macrophage antimicrobial peptides in vitro.

Main Results:

  • The GBS ponA mutant was cleared more rapidly from neonatal rat lungs than the wild-type strain.
  • The ponA mutant exhibited increased susceptibility to killing by alveolar macrophage antimicrobial peptides (beta-defensin and cathelicidin homologues).
  • Alveolar macrophages secrete antimicrobial peptides that contribute to GBS killing.

Conclusions:

  • PBP1a-mediated resistance to alveolar macrophage antimicrobial peptides is crucial for GBS survival in the neonatal lung.
  • Antimicrobial peptide secretion by alveolar macrophages represents a significant innate defense mechanism against GBS in the airway.

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