Article ; Online: Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii.
Antimicrobial agents and chemotherapy
2015 Volume 59, Issue 3, Page(s) 1680–1689
Abstract: ... drivers of its antibacterial activity and resistance determinants have yet to be precisely defined. Here ... we show that the antibacterial activities of sulbactam vary widely across contemporary A. baumannii ... bacterial species, including Acinetobacter baumannii. The clinical use of sulbactam for A. baumannii ...
| Abstract | Sulbactam is a class A β-lactamase inhibitor with intrinsic whole-cell activity against certain bacterial species, including Acinetobacter baumannii. The clinical use of sulbactam for A. baumannii infections is of interest due to increasing multidrug resistance in this pathogen. However, the molecular drivers of its antibacterial activity and resistance determinants have yet to be precisely defined. Here we show that the antibacterial activities of sulbactam vary widely across contemporary A. baumannii clinical isolates and are mediated through inhibition of the penicillin-binding proteins (PBPs) PBP1 and PBP3, with very low frequency of resistance; the rare pbp3 mutants with high levels of resistance to sulbactam are attenuated in fitness. These results support further investigation of the potential clinical utility of sulbactam. |
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| MeSH term(s) | Acinetobacter baumannii/drug effects ; Anti-Bacterial Agents/pharmacology ; Drug Resistance, Multiple, Bacterial/physiology ; Penicillin-Binding Proteins/antagonists & inhibitors ; Sulbactam/pharmacology | ||||||||||
| Chemical Substances | Anti-Bacterial Agents ; Penicillin-Binding Proteins ; Sulbactam (S4TF6I2330) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2015-03 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 217602-6 | ||||||||||
| ISSN | 1098-6596 ; 0066-4804 | ||||||||||
| ISSN (online) | 1098-6596 | ||||||||||
| ISSN | 0066-4804 | ||||||||||
| DOI | 10.1128/AAC.04808-14 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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