4.7 Article

Penicillin-Binding Protein 7/8 Contributes to the Survival of Acinetobacter baumannii In Vitro and In Vivo

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JOURNAL OF INFECTIOUS DISEASES
卷 199, 期 4, 页码 513-521

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UNIV CHICAGO PRESS
DOI: 10.1086/596317

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  1. US Department of Veterans Affairs
  2. US Army Medical Research Acquisition Activity [W81XWH-05-1-0627]
  3. University at Buffalo Interdisciplinary Research Development Fund

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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.

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