Investigating Sortase A inhibitory potential of herbal compounds using integrated computational and biochemical approaches

IF 2.1 3区 医学 Q2 PARASITOLOGY
Akanksha Haldiya , Himanshi Kain , Saumya Dubey , Sharvari Kulkarni Punde , Pramod Kumar P Gupta , Vijay Kumar Srivastava , Sandeep Kumar Srivastava , S.L. Kothari , Sanket Kaushik
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引用次数: 0

Abstract

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.
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。
细菌的多重耐药性正成为全球健康面临的一项重大挑战,在死亡率、发病率和医疗保健系统的财政压力方面造成了巨大伤害。这些细菌不断获得新的毒力因子和耐药机制,这突出表明了对创新抗菌药物和确定新治疗靶点(如排序酶 A (EfSrtAΔN59))的迫切需要。EfSrtAΔN59 是一种转肽酶,对粪肠球菌(E. faecalis)的粘附性和毒力有重要作用,是破坏生物膜形成--持续感染的关键因素--的一个有吸引力的靶点。本研究探讨了两种天然类黄酮--三水合芦丁和槲皮素--对粪肠球菌 EfSrtAΔN59 和生物膜形成的抑制作用。通过体外酶测定和生物膜定量技术,我们证明这两种化合物能显著降低 EfSrtAΔN59 的活性,从而阻碍细菌生物膜的形成。分子对接和 MD 模拟研究证实,三水芦丁和槲皮素与 EfSrtAΔN59 酶有很强的结合亲和力。经这些化合物处理的细菌培养物中生物膜生物量的显著减少进一步证实了这一点。这些发现凸显了三水合芦丁和槲皮素作为新型抗病毒疗法开发候选药物的潜力,旨在减轻粪肠球菌感染,从而为传统抗生素提供了令人信服的替代品。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Acta tropica
Acta tropica 医学-寄生虫学
CiteScore
5.40
自引率
11.10%
发文量
383
审稿时长
37 days
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.
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