Esterases IroE and Fes Participate in the Protection of Salmonella Against Oxidative Stress

Abstract

Salmonella enterica serotype Typhimurium is the leading cause of foodborne illnesses in the United States causing nearly 1.4 million cases and causes hundreds of millions of cases worldwide each year. A multidrug efflux pump called MacAB is essential for the survival of S. Typhimurium in the presence of reactive oxygen species, including hydrogen peroxide (H2O2), in vitro. We know that the expression of macAB is induced upon exposure to H2O2 and is necessary for the survival of S. Typhimurium in the presence of H2O2. Two esterases, Fes and IroE, produced by Salmonella, degrade enterobactin to linear products including 2,3-dihydroxybenzoylserine trimer (DHBS3), a linear trimer of enterobactin. We found that removing the genes encoding the pump (MacAB) or the iroE and fes esterases, reduces survival of the mutant strains when reactive oxygen species are present. Surprisingly, inserting a functional iroE gene back into the mutant strain lacking both esterases (ΔfesΔiroE) allows S. Typhimurium to survive oxidative stress. From this data we conclude that IroE can restore peroxide resistance to a double mutant lacking both IroE and Fes. In the future, we will determine if Fes can also rescue this double mutant from oxidative stress. These genes and the processes in which they participate are potential targets for the development of novel therapeutics to combat this increasingly antibiotic resistant pathogen.