Rot is a key regulator of Staphylococcus aureus biofilm formation

Joe M. Mootz, Meredith A. Benson, Cortney E. Heim, Heidi A. Crosby, Jeffrey S. Kavanaugh, Paul M. Dunman, Tammy L Kielian, Victor J. Torres, Alexander R. Horswill

Research output: Contribution to journalArticle

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Abstract

Staphylococcus aureus is a significant cause of chronic biofilm infections on medical implants. We investigated the biofilm regulatory cascade and discovered that the repressor of toxins (Rot) is part of this pathway. A USA300 community-associated methicillin-resistant S.aureus strain deficient in Rot was unable to form a biofilm using multiple different assays, and we found rot mutants in other strain lineages were also biofilm deficient. By performing a global analysis of transcripts and protein production controlled by Rot, we observed that all the secreted protease genes were up-regulated in a rot mutant, and we hypothesized that this regulation could be responsible for the biofilm phenotype. To investigate this question, we determined that Rot bound to the protease promoters, and we observed that activity levels of these enzymes, in particular the cysteine proteases, were increased in a rot mutant. By inactivating these proteases, biofilm capacity was restored to the mutant, demonstrating they are responsible for the biofilm negative phenotype. Finally, we tested the rot mutant in a mouse catheter model of biofilm infection and observed a significant reduction in biofilm burden. Thus S.aureus uses the transcription factor Rot to repress secreted protease levels in order to build a biofilm.

Original languageEnglish (US)
Pages (from-to)388-404
Number of pages17
JournalMolecular Microbiology
Volume96
Issue number2
DOIs
StatePublished - Apr 1 2015

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Biofilms
Staphylococcus aureus
Peptide Hydrolases
Phenotype
Methicillin Resistance
Cysteine Proteases
Infection
Transcription Factors
Catheters
Enzymes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Mootz, J. M., Benson, M. A., Heim, C. E., Crosby, H. A., Kavanaugh, J. S., Dunman, P. M., ... Horswill, A. R. (2015). Rot is a key regulator of Staphylococcus aureus biofilm formation. Molecular Microbiology, 96(2), 388-404. https://doi.org/10.1111/mmi.12943

Rot is a key regulator of Staphylococcus aureus biofilm formation. / Mootz, Joe M.; Benson, Meredith A.; Heim, Cortney E.; Crosby, Heidi A.; Kavanaugh, Jeffrey S.; Dunman, Paul M.; Kielian, Tammy L; Torres, Victor J.; Horswill, Alexander R.

In: Molecular Microbiology, Vol. 96, No. 2, 01.04.2015, p. 388-404.

Research output: Contribution to journalArticle

Mootz, JM, Benson, MA, Heim, CE, Crosby, HA, Kavanaugh, JS, Dunman, PM, Kielian, TL, Torres, VJ & Horswill, AR 2015, 'Rot is a key regulator of Staphylococcus aureus biofilm formation', Molecular Microbiology, vol. 96, no. 2, pp. 388-404. https://doi.org/10.1111/mmi.12943
Mootz JM, Benson MA, Heim CE, Crosby HA, Kavanaugh JS, Dunman PM et al. Rot is a key regulator of Staphylococcus aureus biofilm formation. Molecular Microbiology. 2015 Apr 1;96(2):388-404. https://doi.org/10.1111/mmi.12943
Mootz, Joe M. ; Benson, Meredith A. ; Heim, Cortney E. ; Crosby, Heidi A. ; Kavanaugh, Jeffrey S. ; Dunman, Paul M. ; Kielian, Tammy L ; Torres, Victor J. ; Horswill, Alexander R. / Rot is a key regulator of Staphylococcus aureus biofilm formation. In: Molecular Microbiology. 2015 ; Vol. 96, No. 2. pp. 388-404.
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