Penicillin-binding protein 7/8 contributes to the survival of Acinetobacter baumannii in vitro and in vivo

J Infect Dis. 2009 Feb 15;199(4):513-21. doi: 10.1086/596317.

Abstract

Background: Acinetobacter baumannii is a bacterial pathogen of increasing medical importance. Little is known about genes important for its survival in vivo.

Methods and results: Screening of random transposon mutants of the model pathogen AB307-0294 identified the mutant AB307.27. AB307.27 contained its transposon insertion in pbpG, which encodes the putative low-molecular-mass penicillin-binding protein 7/8 (PBP-7/8). AB307.27 was significantly killed in ascites (P<.001), but its growth in Luria-Bertani broth was similar to that of its parent, AB307-0294 (P=.13). The survival of AB307.27 was significantly decreased in a rat soft-tissue infection model (P<.001) and a rat pneumonia model (P=.002), compared with AB307-0294. AB307.27 was significantly killed in 90% human serum in vitro, compared with AB307-0294 (P<.001). Electron microscopy demonstrated more coccobacillary forms of AB307.27, compared with AB307-0294, suggesting a possible modulation in the peptidoglycan, which may affect susceptibility to host defense factors.

Conclusions: These findings demonstrate that PBP-7/8 contributes to the pathogenesis of A. baumannii. PBP-7/8 either directly or indirectly contributes to the resistance of AB307-0294 to complement-mediated bactericidal activity. An understanding of how PBP-7/8 contributes to serum resistance will lend insight into the role of this low-molecular-mass PBP whose function is poorly understood.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acinetobacter Infections / immunology*
  • Acinetobacter Infections / microbiology*
  • Acinetobacter baumannii / genetics
  • Acinetobacter baumannii / growth & development*
  • Acinetobacter baumannii / pathogenicity
  • Amino Acid Sequence
  • Animals
  • Blood Bactericidal Activity
  • Complement System Proteins / immunology
  • Computer Simulation
  • DNA Transposable Elements
  • Data Interpretation, Statistical
  • Disease Models, Animal
  • Humans
  • Microscopy, Electron, Transmission
  • Molecular Sequence Data
  • Mutation
  • Penicillin-Binding Proteins / chemistry
  • Penicillin-Binding Proteins / genetics
  • Penicillin-Binding Proteins / metabolism
  • Penicillin-Binding Proteins / physiology*
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Bacterial / microbiology
  • Rats
  • Soft Tissue Infections / immunology
  • Soft Tissue Infections / microbiology
  • Urine / microbiology

Substances

  • DNA Transposable Elements
  • Penicillin-Binding Proteins
  • Complement System Proteins