Journal of Biotechnology & Biomaterials
Open Access

Abstract

Infectious diseases caused by multidrug resistant pathogens are the world�s greatest challenge posing a major threat to human health. In present day scenario, selection pressure has contributed much towards the acquisition and spread of resistance. A continual battle between humans and multitude of infectious organisms are well documented. As antimicrobial usage increased, so did the level and complexity of resistance mechanisms. An urban river water environment like Yamuna highly influenced by anthropogenic activities is a rich reservoir of diverse ESBLs-producing bacteria and ESBLs genes, in particular blaCTX-M. Screening of water samples identified a novel variant of blaCTX-M gene showing maximum homology to members of CTX-M-group-25 particularly blaCTX-M-78. With positive amplification for blaTEM-116 and merP gene, the isolate was tolerant to high concentration of antibiotics with different mode of action and to heavy metals. Molecular modelling and docking with substrate cefotaxime revealed small catalytic pocket similar to classical TEM-1 and SHV-1 genes but well defined hydrolytic activity with high negative interaction energy possibly due to presence of substitutions leading to specific interactions may be accountable for high catalytic efficiency similar to CTX-M-9 that have broad active site. Ser237 and Arg276 responsible for high substrate specificity acting co-operatively to promote hydrolysis through structural alterations of active site and better accommodating the larger cefotaxime molecule was evident. The blaCTX-M-152 obtained from river Yamuna isolate of Klebsiella georgiana is believed to be progenitor of CTX-M-group-25 genes with residues having higher stability and broad spectrum hydrolytic efficacy. The studies of varied active sites giving information about the catalytic interactions are good templates for better wide range inhibitor discovery.

Biography

Email: azammudsser@gmail.com