The electron transport chain (ETC) delivers electrons from many substrates to reduce molecular oxygen to water. ETC accomplishes the stepwise transfer of electrons through series of protein complexes conferring oxidation‐reduction reactions with concomitant transport of p roton across membrane, g enerating a proton g radient which leads ATP s ynthesis b y F0F1ATPase. Bacterial ETC initiates with oxidation of NADH by NADH dehydrogenase complex (complex I). Therefore, damage of complex I leads to insufficient function of ETC and accumulation of NADH inside the cell. Contribution of ETC activity and its consequent changes of NADH levels to bacterial damage response against reactive oxygen and nitrogen species (ROS/RNS) has been poorly understood. In this study, by constructing ndh mutant Salmonella lacking complex I NADH dehydrogenase 2, we evaluated the effect of ETC deficiency to bacterial resistance against ROS and RNS. The growth of ndh mutant Salmonella is impaired in the culture media containing hydrogen peroxide, but rather accelerates in the media containing nitric oxide donors. Data suggest that redox potential of NADH accumulated inside the cell by ETC blockage may affect inversely to bacterial resistance against reactive oxygen species and reactive nitrogen species.

Biological organisms require iron for optimal metabolism. Intracellular pathogens also must secure iron especially during infection of animal hosts expressing NRAMP(natural resistance-associated macrophage protein), a transporter protein sequestering metal ions from pathogens. This study shows that extracytoplasmic function sigma factor σE is required for Salmonella virulence in NRAMP1-expressing mice, and further shows that iron deprivation turns on σE expression of Salmonella. The virulence of σE -deficient Salmonella is completely attenuated in C3H/HeN mice while wild type Salmonella kills all mice. Addition of an iron-chelator DTPA(Diethylene triamine pentaacetic acid) to culture media induces σE expression of Salmonella, but iron supplementation abrogates this induction. These findings suggest that iron limitation in host macrophages can trigger σE -dependent virulence system of Salmonella that may include bacterial iron homeostasis.

Intracellular pathogens must maintain redox homeostasis against the antimicrobial actions of reactive oxygen and nitrogen species produced by host cells. This study proves that glutathione is required to promote survival of an enteric pathogen Salmonella under the conditions producing reactive oxygen or nitrogen species. Glutathione is the non-protein thiol compound distributed in a variety of organisms and possesses strong electron-donating capability to reduce intracellular redox environment. To examine the role of glutathione on Salmonella redox homeostasis under oxidative and nitrosative stress conditions, gshB gene encoding glutathione synthetase was mutated by the one-step PCR inactivation method. The growth of gshB mutant Salmonella producing virtually no glutathione was greatly impaired in the culture media containing either hydrogen peroxide or nitric oxide donors. The results suggest that physiological levels of glutathione can provide a fundamental capability to maintain redox homeostasis for Salmonella in surviving oxidizing conditions of host cells.