Department of Biochemistry, Central University of Rajasthan, Bandarsindri, Ajmer, -305817, India.
Department of Biochemistry, Central University of Rajasthan, Bandarsindri, Ajmer, -305817, India.
Infect Genet Evol. 2018 Dec;66:57-65. doi: 10.1016/j.meegid.2018.09.010. Epub 2018 Sep 15.
Nosocomial infections are caused by ESKAPE (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and E. cloacae) pathogens, and their co-existence is associated with their ability to survive in the hospital setup. They may produce molecules, which helps in the better survival of one ESKAPE pathogens over other. We have identified all secondary metabolite gene clusters in six ESKAPE pathogens and predicted antimicrobial and anti-biofilm properties of their product secondary metabolites. To validate our model, we have taken the secondary metabolites of ESKAPE pathogens and studied their interaction with diguanylate cyclase (involved in quorum sensing) and biofilm-associated protein (involved in biofilm formation) of Acinetobacter baumannii. Results suggest the presence of differential secondary metabolites in all ESKAPE pathogens with only three common non-antimicrobial secondary metabolites. Out of twenty-three antimicrobial secondary metabolites, TP-1161, nosiheptide and meilingmycin, showed the best antimicrobial activity and nineteen showed high anti-biofilm activity. Interaction study showed that secondary metabolites produced by other ESKAPE pathogens (non-Acinetobacter) have very good interaction with diguanylate cyclase and biofilm-associated protein of A. baumannii. This concludes that better survival of these ESKAPE pathogens in hospital setup can be correlated with differential production of antimicrobial secondary metabolites. The present study also investigates the molecular mechanism of the competition of different pathogens living in similar hospital setup (similar habitat). Therefore, the present study will initiate research that might lead to the discovery of antibiotics from one ESKAPE pathogen that controls the infection of other ESKAPE pathogens or other pathogens.
医院获得性感染是由 ESKAPE（屎肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和阴沟肠杆菌）病原体引起的，它们的共存与其在医院环境中生存的能力有关。它们可能产生有助于一种 ESKAPE 病原体比其他病原体更好地生存的分子。我们已经确定了六种 ESKAPE 病原体中的所有次级代谢物基因簇，并预测了它们产物次级代谢物的抗菌和抗生物膜特性。为了验证我们的模型，我们已经提取了 ESKAPE 病原体的次级代谢物，并研究了它们与鲍曼不动杆菌的二鸟苷酸环化酶（参与群体感应）和生物膜相关蛋白（参与生物膜形成）的相互作用。结果表明，所有 ESKAPE 病原体中都存在差异次级代谢物，只有三种常见的非抗菌次级代谢物。在二十三种抗菌次级代谢物中，TP-1161、诺西肽和美满霉素表现出最好的抗菌活性，十九种表现出高抗生物膜活性。相互作用研究表明，其他 ESKAPE 病原体（非鲍曼不动杆菌）产生的次级代谢物与鲍曼不动杆菌的二鸟苷酸环化酶和生物膜相关蛋白有很好的相互作用。这表明这些 ESKAPE 病原体在医院环境中更好的生存能力可以与抗菌次级代谢物的差异产生相关。本研究还研究了生活在类似医院环境（相似栖息地）中的不同病原体之间竞争的分子机制。因此，本研究将启动从一种 ESKAPE 病原体中发现控制其他 ESKAPE 病原体或其他病原体感染的抗生素的研究。
