Repurposing a drug to punish carbapenem-resistant <i>Acinetobacter baumannii</i>.

ABSTRACT: The OXA β-lactamases in Acinetobacter baumannii represent a primary mechanism for resistance to the carbapenems, a class of antibiotics that represent a last line for treatment. In a screen of an U.S. Food and Drug Administration (FDA)-approved drug library, we identified fendiline, a calcium channel blocker, had significantly more antimicrobial activity against OXA-23 expressing cells. Genetic and proteomic studies revealed that fendiline inhibited the essential lipoprotein trafficking pathway (Lol) in both A. baumannii (LolFD) and Escherichia coli (LolCDE). We demonstrate that OXA-23 is an outer membrane lipoprotein and its overexpression resulted in increased lethality in lolFD-depleted A. baumannii. Our results indicate that overexpression of the OXA-

SUBMITTER: Colquhoun JM 

PROVIDER: S-EPMC12184509 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature