The Spx regulator modulates stress responses and virulence in Enterococcus faecalis

Jessica K Kajfasz; Jorge E Mendoza; Anthony O Gaca; James H Miller; Kristy A Koselny; Marcia Giambiagi-Demarval; Melanie Wellington; Jacqueline Abranches; José A Lemos

doi:10.1128/IAI.00026-12

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The Spx regulator modulates stress responses and virulence in Enterococcus faecalis

Journal article

Open access

Peer reviewed

The Spx regulator modulates stress responses and virulence in Enterococcus faecalis

Jessica K Kajfasz, Jorge E Mendoza, Anthony O Gaca, James H Miller, Kristy A Koselny, Marcia Giambiagi-Demarval, Melanie Wellington, Jacqueline Abranches and José A Lemos

Infection and immunity, Vol.80(7), pp.2265-2275

07/2012

DOI: 10.1128/IAI.00026-12

PMCID: PMC3416481

PMID: 22508863

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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.

Anaerobiosis

Enterococcus faecalis - drug effects

Reactive Oxygen Species - metabolism

Oxidative Stress

Humans

Virulence

Oxidants - metabolism

Stress, Physiological

Gene Expression Profiling

Reactive Oxygen Species - toxicity

Peritonitis - pathology

Peritonitis - microbiology

Gene Deletion

Foreign Bodies - complications

Macrophages - immunology

Macrophages - microbiology

Disease Models, Animal

Enterococcus faecalis - pathogenicity

Aerobiosis

Enterococcus faecalis - genetics

Oxidants - toxicity

Microbial Viability

Transcription Factors - genetics

Transcription Factors - metabolism

Animals

Anti-Bacterial Agents - pharmacology

Mice

Mice, Inbred BALB C

Gene Expression Regulation, Bacterial

Enterococcus faecalis - physiology

Details

Title: Subtitle: The Spx regulator modulates stress responses and virulence in Enterococcus faecalis
Creators: Jessica K Kajfasz - Center for Oral Biology, University of Rochester Medical Center, Rochester, New York, USA
Jorge E Mendoza
Anthony O Gaca
James H Miller
Kristy A Koselny
Marcia Giambiagi-Demarval
Melanie Wellington
Jacqueline Abranches
José A Lemos
Resource Type: Journal article
Publication Details: Infection and immunity, Vol.80(7), pp.2265-2275
DOI: 10.1128/IAI.00026-12
PMID: 22508863
PMCID: PMC3416481
ISSN: 0019-9567
eISSN: 1098-5522
Grant note: R25 GM064133 / NIGMS NIH HHS T90 DE021985 / NIDCR NIH HHS R01 DE019783 / NIDCR NIH HHS T32 DE007202 / NIDCR NIH HHS DE019783 / NIDCR NIH HHS KL2 RR024136 / NCRR NIH HHS T32DE007202 / NIDCR NIH HHS
Language: English
Date published: 07/2012
Academic Unit: Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9984093354302771

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