The Staphylococcus aureus ArlRS two-component system regulates virulence factor expression through MgrA

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • University of Colorado Denver
  • University of Iowa
  • Department of Veterans Affairs

Details

Original languageEnglish (US)
Pages (from-to)103-122
Number of pages20
JournalMolecular microbiology
Volume113
Issue number1
StatusPublished - Jan 1 2020
Peer-reviewedYes

Abstract

The Gram-positive bacterium, Staphylococcus aureus, is a versatile pathogen that can sense and adapt to a wide variety of environments within the human host, in part through its 16 two-component regulatory systems. The ArlRS two-component system has been shown to affect many cellular processes in S. aureus, including autolysis, biofilm formation, capsule synthesis and virulence. Yet the molecular details of this regulation remained largely unknown. We used RNA sequencing to identify the ArlRS regulon, and found 70% overlap with that of the global regulator MgrA. These genes included cell wall-anchored adhesins (ebh, sdrD), polysaccharide and capsule synthesis genes, cell wall remodeling genes (lytN, ddh), the urease operon, genes involved in metal transport (feoA, mntH, sirA), anaerobic metabolism genes (adhE, pflA, nrdDG) and a large number of virulence factors (lukSF, lukAB, nuc, gehB, norB, chs, scn and esxA). We show that ArlR directly activates expression of mgrA and identify a probable ArlR-binding site (TTTTCTCAT-N4-TTTTAATAA). A highly similar sequence is also found in the spx P2 promoter, which was recently shown to be regulated by ArlRS. We also demonstrate that ArlS has kinase activity toward ArlR in vitro, although it has slower kinetics than other similar histidine kinases.

Citation formats

APA

Crosby, H. A., Tiwari, N., Kwiecinski, J. M., Xu, Z., Dykstra, A., Jenul, C., ... Horswill, A. R. (2020). The Staphylococcus aureus ArlRS two-component system regulates virulence factor expression through MgrA. Molecular microbiology, 113(1), 103-122. https://doi.org/10.1111/mmi.14404

Harvard

Crosby, HA, Tiwari, N, Kwiecinski, JM, Xu, Z, Dykstra, A, Jenul, C, Fuentes, EJ & Horswill, AR 2020, 'The Staphylococcus aureus ArlRS two-component system regulates virulence factor expression through MgrA', Molecular microbiology, vol. 113, no. 1, pp. 103-122. https://doi.org/10.1111/mmi.14404