Redox Balance via Lactate Dehydrogenase Is Important for Multiple Stress Resistance and Virulence in Enterococcus faecalis

Enterococcus faecalis is a highly stress resistant opportunistic pathogen. The intrinsic ruggedness of this bacterium is supposed to be the basis of its capacity to colonize the hostile environments of hospitals and to cause several kinds of infections. We show in this work that general resistance to very different environmental stresses depends on the ability of E. faecalis to maintain re-dox balance via lactate dehydrogenase (LDH). Furthermore, LDH-deficient mutants are less successful than the wild type at colo-nizing host organs in a murine model of systemic infection. Taken together, our results, as well as those previously published for Staphylococcus aureus (A. R. Richardson, S. J. Libby, and F. C. Fang, Science 319:1672–1676, 2008), identify LDH as an attractive drug target. These drugs may have additional applications, as in the fight against glycopeptide antibiotic-resistant bacteria and even cancer. Enterococcus faecalis is an intestinal resident of humans andmany animals and is amajor cause of severe nosocomial infec-tions that are difficult to treat due to intrinsic and acquired resis-tances to major classes of antibiotics. It is a homofermentative lactic acid bacterium that uses mainly the Embden-Meyerhoff-Parnas (glycolysis) pathway for the catabolism of glucose or re-lated carbohydrates (1). The dominant end product of fermenta-tion under these conditions is lactate (2, 3). Reduction of th