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没食子酸抑制金黄色葡萄球菌 RecA 蛋白功能:在对抗细菌抗生素耐药性中的作用。

Gallic acid inhibits Staphylococcus aureus RecA protein functions: Role in countering antibiotic resistance in bacteria.

机构信息

Department of Microbiology and Fermentation 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.

出版信息

J Appl Microbiol. 2024 Jun 3;135(6). doi: 10.1093/jambio/lxad227.

Abstract

AIM

Recombinase RecA and its homologs play a key role in homologous recombination DNA repair and revive stalled replication fork DNA synthesis. RecA plays an essential role in the evolution of antibiotic-resistant strains via stress-induced DNA repair mechanisms during the SOS response. Accordingly, RecA has become an attractive target to slow down antibiotic resistance rates and prevent mutations in pathogenic bacterial species.

METHODS AND RESULTS

We employed RecA conserved activities: DNA binding, displacement loop formation, strand exchange, ATP hydrolysis, and LexA cleavage, to elucidate the inhibitory role of gallic acid on Staphylococcus aureus RecA functions. Gallic acid inhibition of the SOS response by western blot analysis and its antibacterial activity were measured. The gallic acid inhibited all the canonical activities of S. aureus RecA protein.

CONCLUSION

The natural phenolic compound gallic acid interferes with RecA protein DNA complex formation and inhibits activities such as displacementloop formation, strand exchange reaction, ATP hydrolysis, and coprotease activity of S. aureus. Additionally, gallic acid can obstruct ciprofloxacin-induced RecA expression and eventually confer the inhibitory role of gallic acid in the SOS survival mechanism in S. aureus.

摘要

目的

重组酶 RecA 及其同源物在同源重组 DNA 修复和恢复停滞复制叉 DNA 合成中发挥关键作用。RecA 通过 SOS 反应期间应激诱导的 DNA 修复机制在抗生素耐药菌株的进化中发挥重要作用。因此,RecA 已成为减缓抗生素耐药率和防止致病性细菌物种突变的有吸引力的靶标。

方法和结果

我们利用 RecA 的保守活性:DNA 结合、置换环形成、链交换、ATP 水解和 LexA 切割,阐明了没食子酸对金黄色葡萄球菌 RecA 功能的抑制作用。通过 Western blot 分析和抗菌活性测定了没食子酸对 SOS 反应的抑制作用。没食子酸抑制了金黄色葡萄球菌 RecA 蛋白的所有典型活性。

结论

天然酚类化合物没食子酸干扰 RecA 蛋白 DNA 复合物的形成,并抑制置换环形成、链交换反应、ATP 水解和金黄色葡萄球菌的共蛋白酶活性等活性。此外,没食子酸可以阻碍环丙沙星诱导的 RecA 表达,最终赋予没食子酸在金黄色葡萄球菌 SOS 存活机制中的抑制作用。

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