Pinheiro Patrícia Gonçalves, Santiago Gilvandete Maria Pinheiro, da Silva Francisco Erivaldo Freitas, de Araújo Ana Carolina Justino, de Oliveira Cícera Rejane Tavares, Freitas Priscilla Ramos, Rocha Janaína Esmeraldo, Neto José Bezerra de Araújo, da Silva Maria Milene Costa, Tintino Saulo Relison, Siyadatpanah Abolghasem, Norouzi Roghayeh, Dashti Saeid, Wilairatana Polrat, Coutinho Henrique Douglas Melo, da Costa José Galberto Martins
Departamento de Química Biológica, Programa de Pos-Graduação em Química Biológica, Universidade Regional do Cariri.
Programa de Pós-Graduação em Química, Centro de Ciências, Universidade Federal do Ceará.
Biotechnol Rep (Amst). 2022 Mar 4;34:e00717. doi: 10.1016/j.btre.2022.e00717. eCollection 2022 Jun.
Bacterial resistance to multiple drugs has recently emerged as a serious health problem. Concomitantly, the characterization of new substances with potential antimicrobial activity has been less frequent in the drug development industry. The overexpression of genes encoding efflux pumps that expel antimicrobial drugs from the intracellular environment, lowering these to subinhibitory concentrations, are among the resistance mechanisms predisposing microorganisms to high drug resistance. is a bacterium found in the normal microbiota of the skin and mucous membranes, and is an opportunistic microorganism capable of causing infections with high rates of morbidity and mortality. TetK is an efflux pump characterized by its ability to provide bacterial resistance to antibiotics from the tetracycline class. This study aimed to evaluate the inhibitory effect of ferulic acid and four of its esterified derivatives against resistant strains.
Ferulic acid derivatives were obtained by esterification and then characterized by hydrogen and carbon-13 nuclear magnetic resonance analysis. The minimum inhibitory concentrations (MIC) of ferulic acid and its esterified derivatives, ethidium bromide, and antibiotics were obtained using the microdilution test, while the efflux pump inhibition test was conducted by examining reduction in the MICs.
Propylferulate was seen to reduce the minimum inhibitory concentration (MIC) of both the control substance ethidium bromide and the tested antibiotic, indicating that this compound is promising for the use of efflux pump inhibition of IS-58 strains.
This study provides strong evidence that the molecular basis for this activity is potentially due to the MsrA and TetK efflux pumps. However, further investigations are necessary to prove this hypothesis and elucidate the potentiating mechanism of the modulatory effect.
细菌对多种药物的耐药性最近已成为一个严重的健康问题。与此同时，在制药行业中，具有潜在抗菌活性的新物质的表征变得不那么频繁。编码外排泵的基因过表达可将抗菌药物从细胞内环境中排出，使其降至亚抑制浓度，这是使微生物易产生高耐药性的耐药机制之一。表皮葡萄球菌是一种存在于皮肤和粘膜正常微生物群中的细菌，是一种能够引起高发病率和死亡率感染的机会性微生物。TetK是一种外排泵，其特点是能够使细菌对四环素类抗生素产生耐药性。本研究旨在评估阿魏酸及其四种酯化衍生物对耐药表皮葡萄球菌菌株的抑制作用。
通过酯化反应获得阿魏酸衍生物，然后通过氢和碳-13核磁共振分析对其进行表征。使用微量稀释试验获得阿魏酸及其酯化衍生物、溴化乙锭和抗生素的最低抑菌浓度（MIC），而通过检测MIC的降低来进行外排泵抑制试验。
丙基阿魏酸酯可降低对照物质溴化乙锭和受试抗生素的最低抑菌浓度（MIC），表明该化合物在抑制IS-58菌株外排泵方面具有应用前景。
本研究提供了强有力的证据，表明这种活性的分子基础可能归因于MsrA和TetK外排泵。然而，需要进一步的研究来证实这一假设并阐明调节作用的增强机制。
