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

Heidi A Crosby; Nitija Tiwari; Jakub M Kwiecinski; Zhen Xu; Allison Dykstra; Christian Jenul; Ernesto J Fuentes; Alexander R Horswill

doi:10.1111/mmi.14404

Back

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

Journal article

Peer reviewed

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

Heidi A Crosby, Nitija Tiwari, Jakub M Kwiecinski, Zhen Xu, Allison Dykstra, Christian Jenul, Ernesto J Fuentes and Alexander R Horswill

Molecular microbiology, Vol.113(1), pp.103-122

01/2020

DOI: 10.1111/mmi.14404

PMCID: PMC7175635

PMID: 31618469

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/7175635View

Open Access

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-N -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.

Bacterial Proteins - genetics

Bacterial Proteins - metabolism

DNA, Bacterial

Gene Expression Regulation, Bacterial

Protein Kinases - genetics

Protein Kinases - metabolism

Staphylococcus aureus - genetics

Staphylococcus aureus - metabolism

Staphylococcus aureus - pathogenicity

Virulence

Virulence Factors - genetics

Virulence Factors - metabolism

Details

Title: Subtitle: The Staphylococcus aureus ArlRS two-component system regulates virulence factor expression through MgrA
Creators: Heidi A Crosby - University of Colorado Denver
Nitija Tiwari - Roy J. and Lucille A. Carver College of Medicine
Jakub M Kwiecinski - University of Colorado Denver
Zhen Xu - University of Iowa
Allison Dykstra - Roy J. and Lucille A. Carver College of Medicine
Christian Jenul - University of Colorado Denver
Ernesto J Fuentes - University of Iowa
Alexander R Horswill - University of Colorado Denver
Resource Type: Journal article
Publication Details: Molecular microbiology, Vol.113(1), pp.103-122
DOI: 10.1111/mmi.14404
PMID: 31618469
PMCID: PMC7175635
NLM abbreviation: Mol Microbiol
ISSN: 0950-382X
eISSN: 1365-2958
Grant note: P01 AI083211 / NIAID NIH HHS R21 AI135305 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS R01 AI141490 / NIAID NIH HHS
Language: English
Date published: 01/2020
Academic Unit: Biochemistry and Molecular Biology; Medicine Administration
Record Identifier: 9984288719802771

Metrics

20 Record Views

83 Times Cited - Web of Science

See more details