{"title":"利用综合计算和生物化学方法研究草药化合物的 Sortase A 抑制潜力。","authors":"Akanksha Haldiya , Himanshi Kain , Saumya Dubey , Sharvari Kulkarni Punde , Pramod Kumar P Gupta , Vijay Kumar Srivastava , Sandeep Kumar Srivastava , S.L. Kothari , Sanket Kaushik","doi":"10.1016/j.actatropica.2024.107430","DOIUrl":null,"url":null,"abstract":"<div><div>Multi-drug resistance in bacteria is emerging as a major global health challenge, causing substantial harm in terms of mortality, morbidity, and financial strain on healthcare systems. These bacteria are constantly acquiring new virulence factors and drug-resistance mechanisms, which highlights the critical need for innovative antimicrobial medicines and identification of new therapeutic targets, such as Sortase A (EfSrtA<sub>ΔN59</sub>). EfSrtA<sub>ΔN59</sub>, a transpeptidase significant for the adhesion and virulence of <em>Enterococcus faecalis</em> (<em>E. faecalis</em>), presents an attractive target for disrupting biofilm formation—a key factor in persistent infections. This study investigates the inhibitory effects of two natural flavonoids- Rutin Trihydrate and Quercetin, on EfSrtA<sub>ΔN59</sub> and biofilm formation in <em>E. faecalis</em>. With <em>in vitro</em> enzymatic assays and biofilm quantification techniques, we demonstrate that both compounds significantly attenuate EfSrtA<sub>ΔN59</sub> activity, thereby hindering bacterial biofilm formation. Rutin Trihydrate and Quercetin exhibited strong binding affinities to the EfSrtA<sub>ΔN59</sub> enzyme, as confirmed by molecular docking and MD simulation studies. This was further substantiated by a notable reduction in biofilm biomass in bacterial cultures treated with these compounds. These findings highlight the potential of Rutin Trihydrate and Quercetin as promising candidates for the development of novel anti-virulence therapies aimed at mitigating <em>E. faecalis</em> infections, thereby offering a compelling alternative to traditional antibiotics.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Investigating Sortase A inhibitory potential of herbal compounds using integrated computational and biochemical approaches\",\"authors\":\"Akanksha Haldiya , Himanshi Kain , Saumya Dubey , Sharvari Kulkarni Punde , Pramod Kumar P Gupta , Vijay Kumar Srivastava , Sandeep Kumar Srivastava , S.L. Kothari , Sanket Kaushik\",\"doi\":\"10.1016/j.actatropica.2024.107430\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Multi-drug resistance in bacteria is emerging as a major global health challenge, causing substantial harm in terms of mortality, morbidity, and financial strain on healthcare systems. These bacteria are constantly acquiring new virulence factors and drug-resistance mechanisms, which highlights the critical need for innovative antimicrobial medicines and identification of new therapeutic targets, such as Sortase A (EfSrtA<sub>ΔN59</sub>). EfSrtA<sub>ΔN59</sub>, a transpeptidase significant for the adhesion and virulence of <em>Enterococcus faecalis</em> (<em>E. faecalis</em>), presents an attractive target for disrupting biofilm formation—a key factor in persistent infections. This study investigates the inhibitory effects of two natural flavonoids- Rutin Trihydrate and Quercetin, on EfSrtA<sub>ΔN59</sub> and biofilm formation in <em>E. faecalis</em>. With <em>in vitro</em> enzymatic assays and biofilm quantification techniques, we demonstrate that both compounds significantly attenuate EfSrtA<sub>ΔN59</sub> activity, thereby hindering bacterial biofilm formation. Rutin Trihydrate and Quercetin exhibited strong binding affinities to the EfSrtA<sub>ΔN59</sub> enzyme, as confirmed by molecular docking and MD simulation studies. This was further substantiated by a notable reduction in biofilm biomass in bacterial cultures treated with these compounds. These findings highlight the potential of Rutin Trihydrate and Quercetin as promising candidates for the development of novel anti-virulence therapies aimed at mitigating <em>E. faecalis</em> infections, thereby offering a compelling alternative to traditional antibiotics.</div></div>\",\"PeriodicalId\":7240,\"journal\":{\"name\":\"Acta tropica\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-10-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta tropica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0001706X24003115\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PARASITOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta tropica","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0001706X24003115","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PARASITOLOGY","Score":null,"Total":0}
Investigating Sortase A inhibitory potential of herbal compounds using integrated computational and biochemical approaches
Multi-drug resistance in bacteria is emerging as a major global health challenge, causing substantial harm in terms of mortality, morbidity, and financial strain on healthcare systems. These bacteria are constantly acquiring new virulence factors and drug-resistance mechanisms, which highlights the critical need for innovative antimicrobial medicines and identification of new therapeutic targets, such as Sortase A (EfSrtAΔN59). EfSrtAΔN59, a transpeptidase significant for the adhesion and virulence of Enterococcus faecalis (E. faecalis), presents an attractive target for disrupting biofilm formation—a key factor in persistent infections. This study investigates the inhibitory effects of two natural flavonoids- Rutin Trihydrate and Quercetin, on EfSrtAΔN59 and biofilm formation in E. faecalis. With in vitro enzymatic assays and biofilm quantification techniques, we demonstrate that both compounds significantly attenuate EfSrtAΔN59 activity, thereby hindering bacterial biofilm formation. Rutin Trihydrate and Quercetin exhibited strong binding affinities to the EfSrtAΔN59 enzyme, as confirmed by molecular docking and MD simulation studies. This was further substantiated by a notable reduction in biofilm biomass in bacterial cultures treated with these compounds. These findings highlight the potential of Rutin Trihydrate and Quercetin as promising candidates for the development of novel anti-virulence therapies aimed at mitigating E. faecalis infections, thereby offering a compelling alternative to traditional antibiotics.
期刊介绍:
Acta Tropica, is an international journal on infectious diseases that covers public health sciences and biomedical research with particular emphasis on topics relevant to human and animal health in the tropics and the subtropics.