title: The global regulator ArcA controls resistance to reactive nitrogen and oxygen intermediates in Salmonella enterica serovar Enteritidis.
abstract: Salmonella enterica serovar Enteritidis is a major cause of food-borne diseases associated with consumption of shell eggs. Clinical isolates of S. enterica serovar Enteritidis exhibit a wide spectrum of virulence in mice. A highly virulent isolate (SE2472) was previously shown to be more resistant in vitro than other clinical isolates to acidified sodium nitrite (ASN), a generator of reactive nitrogen and oxygen intermediates (RNI/ROI). SE2472 is also more resistant to S-nitrosoglutathione (GSNO) and hydrogen peroxide (H(2)O(2)) than an ASN-susceptible isolate of S. enterica serovar Enteritidis (SE8743). To investigate the molecular basis for the RNI/ROI resistance of S. enterica serovar Enteritidis, we transformed a genomic DNA library of SE2472 into SE8743. A plasmid clone conferred upon SE8743 enhanced resistance to ASN, GSNO, and H(2)O(2). The DNA insert in the clone encoded ArcA, a global regulator. An arcA mutant of SE2472 was constructed and was found to be more susceptible to GSNO and hydrogen peroxide but not more susceptible to ASN than wild-type SE2472. The susceptibility of the arcA mutant to GSNO and H(2)O(2) was complemented by a plasmid harboring arcA. The coding sequence of the arcA gene in SE2472 and the coding sequence of the arcA gene in SE8743 were identical, suggesting that the difference in resistance to RNI/ROI maybe due to the activity of genes regulated by ArcA. No significant difference in virulence between the wild type and the arcA mutant of SE2472 was observed in mice. These observations show that arcA is essential for resistance of S. enterica serovar Enteritidis to nitrosative and oxidative stress. However, additional genetic loci may contribute to the resistance to RNI/ROI and unusually high virulence for mice of SE2472.
authors.affiliation: Program in Infectious Diseases and Immunity, School of Public Health, University of California at Berkeley, Berkeley, California 94720, USA.
authors.forename: Sangwei
authors.initials: S
authors.lastname: Lu
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Killoran
authors.forename: Ferric C
authors.initials: FC
authors.lastname: Fang
authors.forename: Lee W
authors.initials: LW
authors.lastname: Riley
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D003470:Culture Media; D004269:DNA, Bacterial; D003902:Detergents / Q000494:pharmacology; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000235:genetics; D029968:Escherichia coli Proteins; D015723:Gene Library; D005820:Genetic Testing; D006361:Heating; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016296:Mutagenesis; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009584:Nitrogen / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology*; D010957:Plasmids; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins; D026422:S-Nitrosoglutathione / Q000494:pharmacology*; D012480:Salmonella Infections / Q000382:microbiology; D012477:Salmonella enteritidis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D012965:Sodium Chloride / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D012977:Sodium Nitrite / Q000494:pharmacology*; D014774:Virulence
chemical_list: D001425:Bacterial Outer Membrane Proteins; D003470:Culture Media; D004269:DNA, Bacterial; D003902:Detergents; D029968:Escherichia coli Proteins; D020030:Nitric Oxide Donors; D016877:Oxidants; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; C041610:arcA protein, E coli; D012967:Sodium Dodecyl Sulfate; D012965:Sodium Chloride; D026422:S-Nitrosoglutathione; D006861:Hydrogen Peroxide; D012977:Sodium Nitrite; D009584:Nitrogen