Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 17;122(24):e2423650122.
doi: 10.1073/pnas.2423650122. Epub 2025 Jun 10.

Repurposing a drug to punish carbapenem-resistant Acinetobacter baumannii

Jennifer M Colquhoun  1 , Carter U Brzezinski  2 , Andrew Ji  1 , Julianna Marotta  3   4   5 , Franziska A V Elsen  6 , Robert A Bonomo  7   8   9   10   11   12   13 , Kerrie L May  3   4   5 , Stephan A Sieber  6 , Marcin Grabowicz  3   4   5 , William M Wuest  2 , Philip N Rather  1   3   4   5
Affiliations

Repurposing a drug to punish carbapenem-resistant Acinetobacter baumannii

Jennifer M Colquhoun et al. Proc Natl Acad Sci U S A. .

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-23 β-lactamase in A. baumannii stresses normal lipoprotein trafficking, which makes these cells more susceptible to fendiline. Overall, our data reveal a link between carbapenem resistance and the Lol pathway, which can be leveraged for new drug development.

Keywords: Acinetobacter baumannii; OXA beta-lactamase; antibiotic resistance; drug repurposing; fendiline.

PubMed Disclaimer

Conflict of interest statement

Competing interests statement:The authors declare no competing interest.

References

    1. Antimicrobial Resistance Collaborators, Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 399, 629–655 (2022). - PMC - PubMed
    1. AlAmri A. M., AlQurayan A. M., Sebastian T., AlNimr A. M., Molecular surveillance of multidrug-resistant Acinetobacter baumannii. Curr. Microbiol. 77, 335–342 (2020). - PubMed
    1. Castanheira M., Mendes R. E., Gales A. C., Global epidemiology and mechanisms of resistance of Acinetobacter baumannii-calcoaceticus complex. Clin. Infect. Dis. 76, S166–S178 (2023). - PMC - PubMed
    1. Ma C., McClean S., Mapping global prevalence of Acinetobacter baumannii and recent vaccine development to tackle it. Vaccines (Basel) 9 (2021). - PMC - PubMed
    1. Seifert H., Blondeau J., Lucassen K., Utt E. A., Global update on the in vitro activity of tigecycline and comparators against isolates of Acinetobacter baumannii and rates of resistant phenotypes (2016–2018). J. Glob. Antimicrob. Resist. 31, 82–89 (2022). - PubMed

MeSH terms

LinkOut - more resources