PMID- 26275216
OWN - NLM
STAT- MEDLINE
DCOM- 20160510
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 8
DP  - 2015
TI  - Impact of the Regulators SigB, Rot, SarA and sarS on the Toxic Shock Tst Promoter 
      and TSST-1 Expression in Staphylococcus aureus.
PG  - e0135579
LID - 10.1371/journal.pone.0135579 [doi]
LID - e0135579
AB  - Staphylococcus aureus is an important pathogen manifesting virulence through 
      diverse disease forms, ranging from acute skin infections to life-threatening 
      bacteremia or systemic toxic shock syndromes. In the latter case, the 
      prototypical superantigen is TSST-1 (Toxic Shock Syndrome Toxin 1), encoded by 
      tst(H), and carried on a mobile genetic element that is not present in all S. 
      aureus strains. Transcriptional regulation of tst is only partially understood. 
      In this study, we dissected the role of sarA, sarS (sarH1), RNAIII, rot, and the 
      alternative stress sigma factor sigB (sigmaB). By examining tst promoter regulation 
      predominantly in the context of its native sequence within the SaPI1 
      pathogenicity island of strain RN4282, we discovered that sigmaB emerged as a 
      particularly important tst regulator. We did not detect a consensus sigmaB site 
      within the tst promoter, and thus the effect of sigmaB is likely indirect. We found 
      that sigmaB strongly repressed the expression of the toxin via at least two distinct 
      regulatory pathways dependent upon sarA and agr. Furthermore rot, a member of 
      SarA family, was shown to repress tst expression when overexpressed, although its 
      deletion had no consistent measurable effect. We could not find any detectable 
      effect of sarS, either by deletion or overexpression, suggesting that this 
      regulator plays a minimal role in TSST-1 expression except when combined with 
      disruption of sarA. Collectively, our results extend our understanding of complex 
      multifactorial regulation of tst, revealing several layers of negative 
      regulation. In addition to environmental stimuli thought to impact TSST-1 
      production, these findings support a model whereby sporadic mutation in a few key 
      negative regulators can profoundly affect and enhance TSST-1 expression.
FAU - Andrey, Diego O
AU  - Andrey DO
AD  - Service of Infectious Diseases, University Hospital and Medical School of Geneva, 
      4 rue Gabrielle-Perret-Gentil, CH-1211 Geneva 14, Switzerland.
FAU - Jousselin, Ambre
AU  - Jousselin A
AD  - Department of Microbiology and Molecular Medicine, University Hospital and 
      Medical School of Geneva, 1 rue Michel-Servet, CH-1211 Geneva, Switzerland.
FAU - Villanueva, Maite
AU  - Villanueva M
AD  - Department of Microbiology and Molecular Medicine, University Hospital and 
      Medical School of Geneva, 1 rue Michel-Servet, CH-1211 Geneva, Switzerland.
FAU - Renzoni, Adriana
AU  - Renzoni A
AD  - Service of Infectious Diseases, University Hospital and Medical School of Geneva, 
      4 rue Gabrielle-Perret-Gentil, CH-1211 Geneva 14, Switzerland.
FAU - Monod, Antoinette
AU  - Monod A
AD  - Service of Infectious Diseases, University Hospital and Medical School of Geneva, 
      4 rue Gabrielle-Perret-Gentil, CH-1211 Geneva 14, Switzerland.
FAU - Barras, Christine
AU  - Barras C
AD  - Service of Infectious Diseases, University Hospital and Medical School of Geneva, 
      4 rue Gabrielle-Perret-Gentil, CH-1211 Geneva 14, Switzerland.
FAU - Rodriguez, Natalia
AU  - Rodriguez N
AD  - Department of Microbiology and Molecular Medicine, University Hospital and 
      Medical School of Geneva, 1 rue Michel-Servet, CH-1211 Geneva, Switzerland.
FAU - Kelley, William L
AU  - Kelley WL
AD  - Department of Microbiology and Molecular Medicine, University Hospital and 
      Medical School of Geneva, 1 rue Michel-Servet, CH-1211 Geneva, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150814
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Bacterial Proteins)
RN  - 0 (Bacterial Toxins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enterotoxins)
RN  - 0 (Repressor Proteins)
RN  - 0 (SarA protein, bacterial)
RN  - 0 (SarS protein, Staphylococcus aureus)
RN  - 0 (SigB protein, Bacteria)
RN  - 0 (Sigma Factor)
RN  - 0 (Superantigens)
RN  - 0 (Trans-Activators)
RN  - 0 (enterotoxin F, Staphylococcal)
RN  - 0 (rot protein, Staphylococcus aureus)
SB  - IM
MH  - Bacterial Proteins/genetics/*metabolism
MH  - Bacterial Toxins/genetics/*metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Enterotoxins/genetics/*metabolism
MH  - Gene Expression Regulation, Bacterial/genetics
MH  - Genomic Islands/genetics
MH  - Promoter Regions, Genetic/*genetics
MH  - Repressor Proteins/genetics/*metabolism
MH  - Sigma Factor/genetics/*metabolism
MH  - Staphylococcus aureus/*metabolism
MH  - Superantigens/genetics/*metabolism
MH  - Trans-Activators/genetics/*metabolism
PMC - PMC4537247
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/08/15 06:00
MHDA- 2016/05/11 06:00
PMCR- 2015/08/14
CRDT- 2015/08/15 06:00
PHST- 2014/02/06 00:00 [received]
PHST- 2015/07/24 00:00 [accepted]
PHST- 2015/08/15 06:00 [entrez]
PHST- 2015/08/15 06:00 [pubmed]
PHST- 2016/05/11 06:00 [medline]
PHST- 2015/08/14 00:00 [pmc-release]
AID - PONE-D-14-05733 [pii]
AID - 10.1371/journal.pone.0135579 [doi]
PST - epublish
SO  - PLoS One. 2015 Aug 14;10(8):e0135579. doi: 10.1371/journal.pone.0135579. 
      eCollection 2015.