To study the prevalence of efflux associated resistance in clinical isolates of Pseudomonas aeruginosa and screening of potential Efflux pump inhibitors.

Abstract

Pseudomonas aeruginosa strains that are multidrug resistant (MDR) have been designated as a critical priority pathogen. This bacterium is one of the most common causes of hospital-acquired infections (HAIs), such as pneumonia and septicemia. Patients with respiratory diseases, a weakened immune system, or complex topical injuries such as burn wounds may be at risk from this bacterium. Overexpression of efflux pumps against antibiotics, which extrudes them out of the bacterial cell, is one of P. aeruginosa's resistance mechanisms. It also shows intrinsic resistance against various antibiotics such as tetracyclines because of the presence of efflux pumps like TetA. Efflux pumps belonging to different families have different mode of action and varying substrate specificity. They can act as excellent drug targets. Inhibiting them using EPIs can be an alternate treatment strategy for treating MDR strains In this study, antibiotic susceptibility profiling was done to understand the AMR spectrum in the clinical isolates of P. aeruginosa particularly of north Indian region. MIC reversal in the presence of three universal EPIs (CCCP, 2, 4-DNP and Quercitin) was performed to determine the contribution of efflux mediated resistance. Further, a library of 12 small molecules was screened using EtBr accumulation assay against the clinical isolates for the development of novel therapeutic strategies.