Synergistic Combination of Imipenem and 7-Fluoroindole Inhibits β-lactamases and Biofilm in Carbapenem-resistant Acinetobacter baumannii.

Authors

Anandita Chalana, Vipasha Thakur, Varsha Gupta, Prince Sharma, Neena Capalash

Published in

Journal of applied microbiology. Sep 22, 2025. Epub Sep 22, 2025.

Abstract

Acinetobacter baumannii is a nosocomial opportunistic pathogen responsible for hospital and community-acquired infections. It has been categorised as a high-priority ESKAPE pathogen due to escalating resistance, underscoring the urgent need for effective treatment options. This study explores the use of 7-Fluoroindole (7-FI) as an adjuvant to imipenem for combating Carbapenem-Resistant Acinetobacter baumannii (CRAB).
Clinical strains of A. baumannii were subjected to disc diffusion assay for antibiotic resistance profile, and Fractional Inhibitory Concentration (FIC) of 7-FI was determined with imipenem by checkerboard assay. Expression of β-lactamases, efflux pumps, and outer membrane proteins was determined by qRT-PCR. Biofilm inhibition by 7-FI in combination with imipenem was evaluated by Confocal Laser Scanning Microscopy.
7-FI reduced the MIC of imipenem by 2 to 8-fold in CRAB strains, and also enhanced susceptibility to meropenem. Mechanistically, 7-FI inhibited the β-lactamase activity by 2.3 to 3.8-fold and downregulated the expression of Class B (blaNDM-1) and D (blaOXA-23 and blaOXA-51) β-lactamases. The efflux pump activity was reduced by 2 to 8.6-fold, and expression of efflux pump genes adeB, adeJ, abeM and emrA was also significantly (p < 0.001) downregulated. 7-FI in combination with imipenem inhibited biofilm formation by 80% even at 1 × FIC (1/4 MIC of imipenem and 1/3 MIC of 7-FI).
The combination of 7-FI and imipenem synergistically mitigated carbapenem resistance in A. baumannii by inhibiting the activity of β-lactamases, downregulating the expression of β-lactamases and efflux pumps. The study shows 7-FI as a useful adjuvant to imipenem against CRAB strains.

PMID:
40982215
Bibliographic data and abstract were imported from PubMed on 22 Sep 2025.

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