Center for Bioinformatics, NITTE Deemed to be University, Mangaluru, 575018, India.
Division of Microbiology and Biotechnology, Yenepoya Research Centre, Yenepoya (Deemed to Be University), University Road, Deralakatte, Mangalore, 575018, India.
Microb Pathog. 2023 Oct;183:106314. doi: 10.1016/j.micpath.2023.106314. Epub 2023 Aug 23.
Stenotrophomonas maltophilia, an emerging multidrug-resistant opportunistic bacterium in humans is of major concern for immunocompromised individuals for causing pneumonia and bloodborne infections. This bacterial pathogen is associated with a considerable fatality/case ratio, with up to 100%, when presented as hemorrhagic fever. It is resistant to commonly used drugs as well as to antibiotic combinations. In-silico based functional network analysis is a key approach to get novel insights into virulence and resistance in pathogenic organisms. This study included the protein-protein interaction (PPI) network analysis of 150 specific genes identified for antibiotic resistance mechanism and virulence pathways. Eight proteins, namely, PilL, FliA, Smlt2260, Smlt2267, CheW, Smlt2318, CheZ, and FliM were identified as hub proteins. Further docking studies of 58 selected phytochemicals were performed against the identified hub proteins. Deoxytubulosine and corosolic acid were found to be potent inhibitors of hub proteins of pathogenic S. maltophilia based on protein-ligand interactive study. Further pharmacophore studies are warranted with these molecules to develop them as novel antibiotics against S. maltophilia.
嗜麦芽寡养单胞菌是一种新出现的人机会致病菌,对免疫功能低下者可引起肺炎和血源性感染,引起广泛关注。这种细菌病原体与相当高的病死率/病例比相关,当表现为出血热时,病死率高达 100%。它对常用药物以及抗生素联合用药均具有耐药性。基于计算机的功能网络分析是深入了解病原生物毒力和耐药性的关键方法。本研究包括了对 150 个特定基因的蛋白质-蛋白质相互作用(PPI)网络分析,这些基因被确定与抗生素耐药机制和毒力途径有关。鉴定出 8 个关键蛋白,即 PilL、FliA、Smlt2260、Smlt2267、CheW、Smlt2318、CheZ 和 FliM。进一步对 58 种选定的植物化学物质进行对接研究,针对鉴定出的致病性嗜麦芽寡养单胞菌关键蛋白。基于蛋白-配体相互作用研究,发现脱氧尿苷和柯诺辛酸是致病性嗜麦芽寡养单胞菌关键蛋白的有效抑制剂。需要进一步进行药效团研究,以开发这些分子作为新型抗生素来对抗嗜麦芽寡养单胞菌。