Russo, Thomas A.;
MacDonald, Ulrike;
Beanan, Janet M.;
Olson, Ruth;
MacDonald, Ian J.;
Sauberan, Shauna L.;
Luke, Nicole R.;
Schultz, L. Wayne;
Umland, Timothy C.
Penicillin-Binding Protein 7/8 Contributes to the Survival of Acinetobacter baumannii in vitro and in Vivo
Beschreibung:
<p>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 lowmolecular- 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 = A3). 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 lowmolecular-mass PBP whose function is poorly understood.</p>