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

被引:87
作者
Russo, Thomas A. [1 ,2 ,5 ,6 ,7 ]
MacDonald, Ulrike [6 ]
Beanan, Janet M. [6 ]
Olson, Ruth [6 ]
MacDonald, Ian J. [5 ]
Sauberan, Shauna L. [2 ,6 ]
Luke, Nicole R. [2 ,5 ,6 ]
Schultz, L. Wayne [3 ,4 ,5 ]
Umland, Timothy C. [3 ,4 ,5 ]
机构
[1] SUNY Buffalo, Dept Med, Div Infect Dis, Buffalo, NY 14214 USA
[2] SUNY Buffalo, Dept Microbiol, Buffalo, NY 14214 USA
[3] SUNY Buffalo, Dept Biol Struct, Buffalo, NY 14214 USA
[4] Hauptman Woodward Med Res Inst, Buffalo, NY USA
[5] SUNY Buffalo, Ctr Excellence Bioinformat & Life Sci, Buffalo, NY 14214 USA
[6] SUNY Buffalo, Witebsky Ctr Microbial Pathogenesis, Buffalo, NY 14214 USA
[7] SUNY Buffalo, Vet Adm Western New York Healthcare Syst, Buffalo, NY 14214 USA
关键词
GRAM-NEGATIVE BACILLI; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; SWISS-MODEL; EXTRAINTESTINAL ISOLATE; PEPTIDOGLYCAN SYNTHESIS; RAT MODEL; INFECTIONS; PNEUMONIA; IDENTIFICATION;
D O I
10.1086/596317
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:513 / 521
页数:9
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