Molecular Mechanisms of Multidrug Resistance in Gram-Negative Bacteria
Antimicrobial resistance of bacterial pathogens is one of the biggest challenges we face today in the field of microbiology. Many bacterial cells have gained resistance to every single class of antibiotic in clinical use, often making treatment options very limited. One of the key mechanisms of intrinsic antibiotic resistance of Gram-negative bacteria is through the activity of multidrug efflux pumps belonging to the Resistance-Nodulation-Division (RND) family. These proteins are capable of pumping out various structurally-unrelated antibiotic molecules against the concentration gradient, using the proton-gradient as an energy source. RND pumps have been shown to be responsible for multidrug resistance of a number of Gram-negative bacterial pathogens, and it is becoming increasingly clear that a better understanding of the function and regulation of these pumps is essential in order to design novel and more effective therapeutic measures.
The Kumar Lab is investigating molecular mechanisms underlying the function and regulation of RND pumps in Acinetobacter baumannii and Pseudomonas aeruginosa. Both of these organisms are notorious for causing multidrug resistant infections in immunocompromised individuals. Using novel genetic tools, we are characterizing RND pumps of these two organisms in order to establish their clinical relevance. We are also interested in learning the mechanisms of regulation of RND gene expression in A. baumannii and P. aeruginosa, and are working towards a better understanding of various factors that play a role in their expression and thus the multidrug resistance of these organisms.