1-(1-naphthylmethyl)-piperazine inhibition assay successfully rules out efflux pump overexpression in Acinetobacter baumannii

Author:

Zosim Victor1,Mullié Catherine2,Peltier François2,Potron Anaïs3,Choquet Morgane1

Affiliation:

1. Centre Hospitalier Universitaire Amiens-Picardie

2. University of Picardie Jules Verne

3. Centre Hospitalier Universitaire de Besançon

Abstract

Abstract

Background. Antimicrobial resistance (AMR) in ESKAPE pathogens, notably in carbapenem-resistant Acinetobacter baumannii, is a pressing global health concern, contributing to significant AMR-associated mortality. Efflux pump overexpression plays a crucial role in the multidrug resistance (MDR) of A. baumannii, but the identification of efflux-overexpressing strains remains challenging. Methods. We evaluated the performance of an efflux pump inhibition assay in comparison with RT-qPCR, to assess efflux pump overexpression in a collection of clinical A. baumannii strains. Sixty MDR strains and a wild one were analyzed. Results. The inhibition assay was positive for 34 and negative for 27 strains, respectively. Results were in agreement with RT-qPCR in 67.2% of the tested strains (39/58). Cohen's kappa showed a fair agreement between inhibition assay and RT-qPCR (Cohen’s kappa = 0.37). Inhibition by NMP, but not PAβN, was in moderate agreement with RT-qPCR (Cohen’s kappa = 0.41).Furthermore, gpi alleles were associated with efflux pump overexpression (p = 0.03), suggesting potential links between genetic diversity and efflux pump overexpression. RT-qPCR showed a significant efflux pump overexpression for 4 (16.7%) out of 24 inhibition assay negative strains. Conclusions. Our findings support the ability to reliably rule out efflux pump overexpression in A. baumannii strains displaying a negative result with an inhibition test relying on NMP. However, confirmatory analyses are necessary for strains that test positive.

Publisher

Springer Science and Business Media LLC

Reference29 articles.

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3. WHO TEAM, Antimicrobial Resistance Division, Global Coordination and Partnership, Selection M, IP and, Affordability (2017) Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis [Internet]. World Health Organization (WHO); doi: https://www.who.int/publications/i/item/WHO-EMP-IAU-2017.12

4. Centers for Disease Control and Prevention (U.S.) Antibiotic resistance threats in the United States, 2019 [Internet]. Centers for Disease Control and Prevention (U.S.); 2019 [cited 2023 1]. doi: https://stacks.cdc.gov/view/cdc/82532doi: 10.15620/cdc:82532

5. Global Epidemiology and Mechanisms of Resistance of Acinetobacter baumannii-calcoaceticus Complex;Castanheira M;Clin Infect Dis,2023

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