Exposure to sub-inhibitory ciprofloxacin and nitrofurantoin concentrations increases recA gene expression in uropathogenic Escherichia coli: The role of RecA protein as a drug target

Autor(es)

da Silva Ribeiro, Aghata Cardoso ^[1] ; Brasileiro da Silva Martins, Willames Marcos ^[2] ; da Silva, Adilson Aderito ^[3] ; Gales, Ana Cristina ^[2] ; Galasse Rando, Daniela Goncales ^[4] ; da Rocha Minarini, Luciene Andrade ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Farmaceut, Lab Multidisciplinar Saude & Meio Ambiente, UNIFES, Rua Sao Nicolau, BR-210 Diadema, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Internal Med, Div Infect Dis, Lab Alerta, Escola Paulista Med, UNIFESP, Rua Pedro Toledo 781, Sao Paulom, SP - Brazil

^[3] Univ Presbiteriana Mackenzie, Ctr Ciencias Sociais & Aplicadas, Rua Consolacao 930, Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Farmaceut, Grp Pesquisas Quim Farmaceut, UNIFESP, Rua Sao Nicolau 210, Diadema, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmaceutical Sciences; v. 146, APR 15 2020.
• Citações Web of Science: 0

Resumo

Sub-inhibitory concentrations (sub-MIC) of antimicrobial agents can lead to genetic changes in bacteria, modulating the expression of genes related to bacterial stress and leading to drug resistance. Herein we describe the impact of sub-MIC of ciprofloxacin and nitrofurantoin on three uropathogenic Escherichia coli strains. Disk-diffusion assays with different antimicrobial agents were tested to detect phenotype alterations, and quantitative real-time PCR (qRT-PCR) was performed to analyze the expression of ompF and recA genes. Significant reduction on the susceptibility to ciprofloxacin and nitrofurantoin was detected on disk diffusion test. The qRT-PCR results revealed a 1.2-4.7 increase in recA expression in all E. coli studied, while the ompF expression varied. Because RecA was pointed as an important component to the development of drug resistance, molecular docking studies were performed with three experimentally known inhibitors of this enzyme. These studies aimed to understand the inhibitory binding mode of such compounds. The results confirmed the ADP/ATP binding site as a potential site of inhibitor recognition and a binding mode based on pi-stacking interactions with Tyr103 and hydrogen bonds with Tyr264. These findings can be useful for guiding the search and design of new antimicrobial agents, mainly concerning the treatment of infections with resistant bacterial strains. (AU)

• Processo FAPESP: 12/18741-4 - Caracterização molecular de plasmídeos de amostras clínicas brasileiras carreadoras do gene qnr
• Beneficiário: Luciene Andrade da Rocha Minarini
• Modalidade de apoio: Auxílio à Pesquisa - Regular