Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, Liaoning, China.
Vet Res. 2022 Jan 10;53(1):3. doi: 10.1186/s13567-021-01021-w.
Trueperella pyogenes (T. pyogenes) is an opportunistic pathogen associated with a variety of diseases in many domestic animals. Therapeutic treatment options for T. pyogenes infections are becoming limited due to antimicrobial resistance, in which efflux pumps play an important role. This study aims to evaluate the inhibitory activity of luteolin, a natural flavonoid, on the MsrA efflux pump and investigate its mechanism. The results of antimicrobial susceptibility testing indicated that the susceptibility of msrA-positive T. pyogenes isolates to six macrolides increased after luteolin treatment, while the susceptibility of msrA-negative isolates showed no change after luteolin treatment. It is suspected that luteolin may increase the susceptibility of T. pyogenes isolates by inhibiting MsrA activity. After 1/2 MIC luteolin treatment for 36 h, the transcription level of the msrA gene and the expression level of the MsrA protein decreased by 55.0-97.7% and 36.5-71.5%, respectively. The results of an affinity test showed that the equilibrium dissociation constant (KD) of luteolin and MsrA was 6.462 × 10 M, and hydrogen bonding was predominant in the interaction of luteolin and MsrA. Luteolin may inhibit the ATPase activity of the MsrA protein, resulting in its lack of an energy source. The current study illustrates the effect of luteolin on MsrA in T. pyogenes isolates and provides insight into the development of luteolin as an innovative agent in combating infections caused by antimicrobial-resistant bacteria.
豚鼠气单胞菌（Trueperella pyogenes，T. pyogenes）是一种机会性病原体，与许多家畜的多种疾病有关。由于抗菌药物耐药性的出现，治疗豚鼠气单胞菌感染的治疗选择变得越来越有限，其中外排泵发挥着重要作用。本研究旨在评估天然类黄酮木樨草素对 MsrA 外排泵的抑制活性，并研究其作用机制。抗菌药物敏感性测试结果表明，木樨草素处理后，msrA 阳性豚鼠气单胞菌分离株对 6 种大环内酯类药物的敏感性增加，而 msrA 阴性分离株在木樨草素处理后敏感性没有变化。推测木樨草素可能通过抑制 MsrA 活性来增加豚鼠气单胞菌分离株的敏感性。在 1/2 MIC 木樨草素处理 36 小时后，msrA 基因的转录水平和 MsrA 蛋白的表达水平分别降低了 55.0-97.7%和 36.5-71.5%。亲和性测试结果表明，木樨草素与 MsrA 的平衡解离常数（KD）为 6.462×10-5M，木樨草素与 MsrA 的相互作用以氢键为主。木樨草素可能抑制 MsrA 蛋白的 ATP 酶活性，导致其缺乏能量来源。本研究阐明了木樨草素对豚鼠气单胞菌分离株中 MsrA 的作用，为开发木樨草素作为一种创新药物来对抗抗菌药物耐药菌引起的感染提供了思路。
