The ultimate goal of my research is to develop novel ways of preventing and treating infectious diseases caused by bacteria resistant to multiple antibiotics. These bacteria have become a major problem in the U.S. and abroad, from failed treatment of previously curable diseases to increased hospital costs. There are about 2 million hospital-acquired infections in the U.S. each year, with more than 99,000 deaths occurring mostly due to antibiotic resistant pathogens. World health leaders have described antibiotic resistant pathogens as “nightmare bacteria that pose a catastrophic threat to people in every country in the world”. My laboratory uses a multidisciplinary approach that includes bacterial genetics and biochemistry, molecular biology, gene expression experiments, and “omics” to study multidrug resistance in bacteria. Our current main projects are:
1) Studying the regulation and physiological role of the AcrAB-TolC multidrug efflux pump. This pump is the main multidrug efflux pump in Escherichia coli and many other pathogenic Enterobacteriaceae. The AcrAB-TolC pump effluxes multiple classes of antibiotics, bile salts and other exogenous toxic compounds. A better understanding of its regulation and physiological substrates is essential to develop novel efflux inhibitors capable of restoring antibiotic efficacy.
2) Identification of carbapenem-resistant bacteria and genes. Carbapenems are last resort antibiotics used in healthcare facilities to treat multidrug resistant bacteria. Carbapenem-resistant bacteria, especially Gram-negatives, are often untreatable and are associated with mortality. The CDC has designated them as an urgent threat. Our overall goal is to examine the distribution, frequency and type of carbapenem-resistant bacteria found in different locations to better predict and prevent potential outbreaks in the future. We are especially interested in identifying novel genes and genetic mobile elements conferring resistance to carbapenems.