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Antimicrob Agents Chemother. 2015 Mar;59(3):1680-9. doi: 10.1128/AAC.04808-14. Epub 2015 Jan 5.

Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii.

Author information

1
Infection Innovative Medicines, AstraZeneca R&D Boston, Waltham, Massachusetts, USA.
2
Infection Innovative Medicines, AstraZeneca R&D Boston, Waltham, Massachusetts, USA alita.miller@astrazeneca.com.

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.

PMID:
25561334
PMCID:
PMC4325763
DOI:
10.1128/AAC.04808-14
[Indexed for MEDLINE]
Free PMC Article

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