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

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Penwell WF, Shapiro AB, Giacobbe RA, Gu RF, Gao N, Thresher J, McLaughlin RE, Huband MD, DeJonge BL, Ehmann DE, Miller AA

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

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

PubMed ID

25561334 [ View in PubMed

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Abstract

Sulbactam is a class A beta-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.

DrugBank Data that Cites this Article

Drugs

Ceftazidime

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ceftazidime	Penicillin-binding protein 1A	Protein	Escherichia coli (strain K12)	Yes	Inhibitor	Details
Ceftazidime	Penicillin-binding protein 1B	Protein	Escherichia coli (strain K12)	Yes	Inhibitor	Details
Ceftazidime	Penicillin-binding protein 2	Protein	Escherichia coli (strain K12)	Yes	Inhibitor	Details
Ceftazidime	Peptidoglycan synthase FtsI	Protein	Escherichia coli (strain K12)	Yes	Inhibitor	Details