Session 1C Lectures by Fellows/Associates

Strategies for combating carbapenem resistant Acinetobacter baumannii

Acinetobacter baumannii causes pneumonia, respiratory infections, and urinary tract infections in humans. Phenotyping and genotyping, as well as clinical quantitative proteomics studies, concluded the overproduction of different carbapenem hydrolyzing β-lactamase, efflux pumps, and siderophore receptors in carbapenem-resistant strain. Further, the bacterium also downregulates putative OmpW as well as transporters that decreases the uptake of carbapenem. The differentially expressed proteins were cloned and purified. It is found that the conformational stability of the recombinant protein (like OXA-51) plays a vital role in retaining the function of β-lactamase even under stress conditions. Experimental and bioinformatics studies showed that carbapenem is effectively hydrolyzed by OXA-51. To combat this carbapenem resistant Acinetobacter baumannii different strategies were used. In first strategy, we have reported that PVP-capped AgNPs inhibits the infection of A. baumannii in the human pulmonary epithelial cell, and secondary metabolites of Actinidia deliciosa and Phyllanthus emblica inhibit biofilm and reduces its extra-cellular matrix components in A. baumannii. Hence, we have capped this secondary metabolite on PVP-AgNPs and synthesized a nano-herbal molecule i.e., gallate-polyvinylpyrrolidone capped hybrid silver nanoparticles (G-PVP-AgNPs) that showed good antimicrobial activity against the carbapenem-resistant strain of A. baumannii and involved ROS dependent killing mechanism. In another strategy, In-silico screening, molecular mechanics, molecular dynamics simulation, and experimental validation studies identified ZINC00039089 as an inhibitor for Bap, a biofilm-associated protein, ZINC01155930 as an inhibitor of AdeABC efflux pump, and ZINC01530654 as an inhibitor for RecA protein of A. baumannii. RecA inhibitor is useful to enhance the efficacy of current antibiotics or disinfectants. Therefore, different strategies can be used in combination for combating carbapenem resistant Acinetobacter baumannii.