New tools to mitigate drug resistance in Enterobacteriaceae - Escherichia coli and Klebsiella pneumoniae .

Treatment to common bacterial infections are becoming ineffective of late, owing to the emergence and dissemination of antibiotic resistance globally. Escherichia coli and Klebsiella pneumoniae are the most notorious microorganisms and are among the critical priority pathogens listed by WHO in 2017. These pathogens are the predominant cause of sepsis, urinary tract infections (UTIs), pneumonia, meningitis and pyogenic liver abscess. Concern arises due to the resistance of bacteria to most of the beta lactam antibiotics like penicillin, cephalosporin, monobactams and carbapenems, even to the last resort antibiotics like colistin. Preventing influx by modulation of porins, extruding the antibiotics by overexpression of efflux pumps, mutations of drug targets/receptors, biofilm formation, altering the drug molecules and rendering them ineffective are few resistance mechanisms that are adapted by Enterobacteriaeceae upon exposure to antibiotics. The situation is exacerbated due to the process of horizontal gene transfer (HGT), wherein the genes encoding resistance mechanisms are transferred to the neighbouring bacteria through plasmids/phages/uptake of free DNA. Carbapenemases, other beta lactamases and mcr genes coding for colistin resistance are widely disseminated leading to limited/no therapeutic options against those infections. Development of new antibiotics can be viewed as a possible solution but it involves major investment, time and labour despite which, the bacteria can easily adapt to the new antibiotic and evolve resistance in a relatively short time. Targeting the resistance mechanisms can be one feasible alternative to tackle these multidrug resistant (MDR) pathogens. Removal of plasmid (plasmid curing) causing resistance, use of bacteriophages and bacteriotherapy can be other potential approaches to combat infections caused by MDR E. coli and K. pneumoniae . The present review discusses the efficacies of these therapies in mitigating these infections, which can be potentially used as an adjuvant therapy along with existing antibiotics.