Riparin-B as a Potential Inhibitor of AdeABC Efflux System from Acinetobacter baumannii

Patrícia Virna Sales Leão; Ana Laura da Silva Ferreira; Felipe Araújo de Alcântara Oliveira; Avilnete Belém de Souza Mesquita; José de Sousa Lima-Net; Stanley Juan Chavéz Gutierrez; Carlos Emídio Sampaio Nogueira; Natália Cruz-Martins; Daniel Dias Rufino Arcanjo; Humberto Medeiros Barreto; Josie Haydée Lima Ferreira

doi:10.1155/2023/1780838

Riparin-B as a Potential Inhibitor of AdeABC Efflux System from Acinetobacter baumannii

Evid Based Complement Alternat Med. 2023 Apr 8:2023:1780838. doi: 10.1155/2023/1780838. eCollection 2023.

Affiliations

¹ Laboratory of Research in Microbiology, Department of Parasitology and Microbiology, Federal University of Piaui, Teresina, Piauí, Brazil.
² Department of Pharmacy, Federal University of Piauí, Teresina, Piauí, Brazil.
³ Department of Biological Chemistry, Regional-University of Cariri, Crato, Ceará, Brazil.
⁴ Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, Porto 4200-319, Portugal.
⁵ Institute for Research and Innovation in Health (i3S), University of Porto, Porto 4200-135, Portugal.
⁶ Laboratory of Functional and Molecular Studies on Physiopharmacology (LAFMOL), Department of Biophysics and Physiology, Federal University of Piaui, Teresina, Piauí, Brazil.

Abstract

Acinetobacter baumannii is an important opportunistic pathogen that causes serious health-related infections, especially in intensive care units. The present study aimed to investigate the antimicrobial activity of Riparin-B (Rip-B) alone and in association with norfloxacin against multidrug-resistant clinical isolates of A. baumannii. For this, the minimum inhibitory concentrations were determined by the microdilution method. For the evaluation of resistance-modulating activity, MIC values for antibiotics were determined in the presence or absence of subinhibitory concentrations of Rip-B or chlorpromazine (CPZ). The AdeABC-AdeRS efflux system genes from these isolates were detected by PCR. Docking studies were also carried out to evaluate the interaction of Riparin-B and the AdeABC-AdeRS efflux system. The study was conducted from 2017 to 2019. The results showed that Rip-B showed weak intrinsic activity against the strains tested. On the other hand, Rip-B was able to modulate norfloxacin's response against A. baumannii strains that express efflux pump-mediated resistance. Docking studies provided projections of the interaction between Rip-B and EtBr with the AdeB protein, suggesting that Rip-B acts by competitive inhibition with the drug. Results found by in vitro and in silico assays suggest that Rip-B, in combination with norfloxacin, has the potential to treat infections caused by multidrug-resistant A. baumanni with efflux pump resistance.