RpiRc Is a Pleiotropic Effector of Virulence Determinant Synthesis and Attenuates Pathogenicity in Staphylococcus aureus.
In Staphylococcus aureus, metabolism is intimately linked with virulence determinant biosynthesis, and several metabolite-responsive regulators have been reported to mediate this linkage. S. aureus possesses at least three members of the RpiR family of transcriptional regulators. Of the three RpiR homologs, RpiRc is a potential regulator of the pentose phosphate pathway, which also regulates RNAIII levels. RNAIII is the regulatory RNA of the agr quorum-sensing system that controls virulence determinant synthesis. The effect of RpiRc on RNAIII likely involves other regulators, as the regulators that bind the RNAIII promoter have been intensely studied. To determine which regulators might bridge the gap between RpiRc and RNAIII, sarA, sigB, mgrA, and acnA mutations were introduced into an rpiRc mutant background, and the effects on RNAIII were determined. Additionally, phenotypic and genotypic differences were examined in the single and double mutant strains, and the virulence of select strains was examined using two different murine infection models. The data suggest that RpiRc affects RNAIII transcription and the synthesis of virulence determinants in concert with σ(B), SarA, and the bacterial metabolic status to negatively affect virulence.
Institute of Medical Microbiology and Hygiene, Saarland University Medical Center, Homburg/Saar, Germany rosmarie.gaupp@uks.eu.|School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Rosmarie
R
Gaupp
Institute of Medical Microbiology and Hygiene, Saarland University Medical Center, Homburg/Saar, Germany.
Jessica
J
Wirf
Institute of Anatomy and Cell Biology, Saarland University Medical Center, Homburg/Saar, Germany.
B
B
Wonnenberg
Institute of Medical Microbiology and Hygiene, Saarland University Medical Center, Homburg/Saar, Germany.
Tanja
T
Biegel
Institute of Medical Microbiology and Hygiene, Saarland University Medical Center, Homburg/Saar, Germany.
J
J
Eisenbeis
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
J
J
Graham
Institute of Medical Microbiology and Hygiene, Saarland University Medical Center, Homburg/Saar, Germany.
M
M
Herrmann
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
C Y
CY
Lee
Department of Internal Medicine V-Pulmonology, Allergology, and Respiratory Critical Care Medicine, Saarland University Medical Center, Homburg/Saar, Germany.
C
C
Beisswenger
Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
C
C
Wolz
Institute of Anatomy and Cell Biology, Saarland University Medical Center, Homburg/Saar, Germany.
T
T
Tschernig
Institute of Medical Microbiology and Hygiene, Saarland University Medical Center, Homburg/Saar, Germany.
M
M
Bischoff
School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
G A
GA
Somerville
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D056426:Genetic Loci; D051379:Mice; D009154:Mutation; D009876:Operon; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000401:mortality; D013211:Staphylococcus aureus / Q000502:physiology*; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D012097:Repressor Proteins; D037521:Virulence Factors