title: The Spx regulator modulates stress responses and virulence in Enterococcus faecalis.
abstract: The ability to cope with endogenous or host-generated reactive oxygen species is considered a key virulence attribute of the opportunistic pathogen Enterococcus faecalis, a leading cause of hospital-acquired infections. In this study, we used in silico and mutational analyses to identify and characterize the role of the Spx global regulator in oxidative stress tolerance and virulence in E. faecalis. While the Δspx strain grew as well as the wild-type strain under anaerobic conditions, the mutant strain exhibited impaired growth under aerobic conditions and was highly sensitive to oxidative stress agents. The spx mutant strain was also sensitive to a variety of other stressful conditions, including antibiotic stress and killing by the mouse-derived macrophage cell line J774. Using a murine model of foreign body-associated peritonitis, we demonstrated that the ability of the Δspx strain to colonize the peritoneum and disseminate in the bloodstream was significantly reduced compared to that of the parent strain. Transcriptional analysis revealed that a large number of known oxidative stress genes are under positive control by Spx. Collectively, our results show that Spx is a major stress gene regulator and is implicated in the pathophysiology of E. faecalis. The relationship of Spx to other oxidative stress regulators is also discussed.
authors.affiliation: Center for Oral Biology, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Kajfasz
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Mendoza
authors.forename: Anthony O
authors.initials: AO
authors.lastname: Gaca
authors.forename: James H
authors.initials: JH
authors.lastname: Miller
authors.forename: Kristy A
authors.initials: KA
authors.lastname: Koselny
authors.forename: Marcia
authors.initials: M
authors.lastname: Giambiagi-Demarval
authors.forename: Melanie
authors.initials: M
authors.lastname: Wellington
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Abranches
authors.forename: José A
authors.initials: JA
authors.lastname: Lemos
mesh_terms: D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D013293:Enterococcus faecalis / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D005547:Foreign Bodies / Q000150:complications; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D016877:Oxidants / Q000378:metabolism / Q000633:toxicity; D018384:Oxidative Stress; D010538:Peritonitis / Q000382:microbiology / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; D014157:Transcription Factors