Role of RND Efflux Pumps and Biofilm in Conferring Antimicrobial Resistance

Abstract

Resistant bacteria deploy a diverse array of defense mechanisms to counter the inhibitory effect of antibiotics and help them survive adverse conditions. Efflux pumps and biofilms significantly contribute to the overall AMR phenomenon. While the former contributes to the extrusion of toxic metabolites and antibiotics out of the bacterial planktonic forms, the latter confers protection to the bacterial population per se at a community level. The association of both of these factors in pathogens responsible for nosocomial infections further indicates their significance in the development of multi-drug resistance. newlineThe present work aims to understand the role of the key contributing factors in efflux-mediated and biofilm-driven AMR. The first aspect of the work is based on the structural and functional explorations of efflux pump members belonging to the RND family. The outcomes of this research work shed light on the potential mechanisms of resistance and the possibility of horizontal gene transfer to spread antibiotic resistance. These RND efflux pumps share similar structural organization and overlapping functionalities, despite sharing a diversified sequence homology. Furthermore, explorative research on the characterization of the complex structural and functional aspects of OqxB, the not-so-well-characterized RND efflux pump in Klebsiella pneumoniae, adds significant knowledge to our current understanding of its role in multi-drug efflux and in conferring resistance against different classes of antibiotics, especially fluoroquinolones. newlineAnother aspect of the study is focused on understanding the interplay of factors contributing to biofilm formation in Escherichia coli. The validated in silico platform developed and reported in this work enhances our current understanding of the roles of different pathways, signalling molecules and cellular components, which drive the overall process of biofilm formation in E. coli.