Riparin-B as a Potential Inhibitor of AdeABC Efflux System from Acinetobacter baumannii .
Patrícia Virna Sales LeãoAna Laura da Silva FerreiraFelipe Araújo de Alcântara OliveiraAvilnete Belém de Souza MesquitaJosé de Sousa Lima NetoStanley Juan Chavéz GutierrezCarlos Emídio Sampaio NogueiraNatália Cruz MartinsDaniel Dias Rufino ArcanjoHumberto Medeiros BarretoJosie Haydée Lima FerreiraPublished in: Evidence-based complementary and alternative medicine : eCAM (2023)
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.
Keyphrases
- acinetobacter baumannii
- multidrug resistant
- drug resistant
- gram negative
- pseudomonas aeruginosa
- intensive care unit
- klebsiella pneumoniae
- escherichia coli
- protein protein
- molecular dynamics
- small molecule
- molecular dynamics simulations
- gene expression
- emergency department
- risk assessment
- genome wide
- single cell
- amino acid
- case control