Department of Protein Chemistry and Technology, Council of Scientific & Industrial Research-Central Food Technological Research Institute (CSIR-CFTRI), Mysuru, 570 020, Karnataka, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India.
Department of Protein Chemistry and Technology, Council of Scientific & Industrial Research-Central Food Technological Research Institute (CSIR-CFTRI), Mysuru, 570 020, Karnataka, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India.
Biochem Biophys Res Commun. 2019 Oct 1;517(4):655-661. doi: 10.1016/j.bbrc.2019.07.093. Epub 2019 Aug 13.
Bacterial RecA plays an important role in the evaluation of antibiotic resistance via stress-induced DNA repair mechanism; SOS response. Accordingly, RecA became an important therapeutic target against antimicrobial resistance. Small molecule inhibitors of RecA may prevent adaptation of antibiotic resistance mutations and the emergence of antimicrobial resistance. In our study, we observed that phenolic compound p-Coumaric acid as potent RecA inhibitor. It inhibited RecA driven biochemical activities in vitro such as ssDNA binding, strand exchange, ATP hydrolysis and RecA coprotease activity of E. coli and L. monocytogenes RecA proteins. The mechanism underlying such inhibitory action of p-Coumaric acid involves its ability to interfere with the DNA binding domain of RecA protein. p-Coumaric acid also potentiates the activity of ciprofloxacin by inhibiting drastic cell survival of L. monocytogenes as well as filamentation process; the bacteria defensive mechanism in response to DNA damage. Additionally, it also blocked the ciprofloxacin induced RecA expression leading to suppression of SOS response in L. monocytogenes. These findings revealed that p-Coumaric acid is a potent RecA inhibitor, and can be used as an adjuvant to the existing antibiotics which not only enhance the shelf-life but also slow down the emergence of antibiotic resistance in bacteria.
细菌 RecA 在通过应激诱导的 DNA 修复机制（SOS 反应）评估抗生素耐药性方面发挥着重要作用。因此，RecA 成为了对抗抗菌药物耐药性的重要治疗靶点。RecA 的小分子抑制剂可能会阻止抗生素耐药性突变的适应和抗菌药物耐药性的出现。在我们的研究中，我们观察到酚类化合物对香豆酸是一种有效的 RecA 抑制剂。它在体外抑制 RecA 驱动的生化活性，如单链 DNA 结合、链交换、ATP 水解和大肠杆菌和单核细胞增生李斯特菌 RecA 蛋白的 RecA 共蛋白酶活性。对香豆酸这种抑制作用的机制涉及到它干扰 RecA 蛋白 DNA 结合域的能力。对香豆酸还通过抑制李斯特菌的剧烈细胞存活以及细菌对 DNA 损伤的防御机制（丝状化过程）来增强环丙沙星的活性。此外，它还阻断了环丙沙星诱导的 RecA 表达，从而抑制了李斯特菌中的 SOS 反应。这些发现表明，对香豆酸是一种有效的 RecA 抑制剂，可作为现有抗生素的辅助剂，不仅可以延长保质期，还可以减缓细菌对抗生素耐药性的出现。
