Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice

Rudy Jacquet, Annette E. LaBauve, Lavoisier Akoolo, Shivani Patel, Abdulelah A. Alqarzaee, Tania Wong Fok Lung, Kunal Poorey, Timothy P. Stinear, Vinai C. Thomas, Robert J. Meagher, Dane Parker

Research output: Contribution to journalArticle

Abstract

Staphylococcus aureus is a major human pathogen of the skin. The global burden of diabetes is high, with S. aureus being a major complication of diabetic wound infections. We investigated how the diabetic environment influences S. aureus skin infection and observed an increased susceptibility to infection in mouse models of both type I and type II diabetes. A dual gene expression approach was taken to investigate transcriptional alterations in both the host and bacterium after infection. While analysis of the host response revealed only minor changes between infected control and diabetic mice, we observed that S. aureus isolated from diabetic mice had significant increases in the levels of genes associated with translation and posttranslational modification and chaperones and reductions in the levels of genes associated with amino acid transport and metabolism. One family of genes upregulated in S. aureus isolated from diabetic lesions encoded the Clp proteases, associated with the misfolded protein response. The Clp proteases were found to be partially glucose regulated as well as influencing the hemolytic activity of S. aureus. Strains lacking the Clp proteases ClpX, ClpC, and ClpP were significantly attenuated in our animal model of skin infection, with significant reductions observed in dermonecrosis and bacterial burden. In particular, mutations in clpP and clpX were significantly attenuated and remained attenuated in both normal and diabetic mice. Our data suggest that the diabetic environment also causes changes to occur in invading pathogens, and one of these virulence determinants is the Clp protease system.

Original languageEnglish (US)
Article numbere00163-19
JournalInfection and immunity
Volume87
Issue number5
DOIs
StatePublished - May 1 2019

Fingerprint

Endopeptidase Clp
Statistical Factor Analysis
Virulence
Staphylococcus aureus
Gene Expression
Infection
Skin
Genes
Wound Infection
Diabetes Complications
Post Translational Protein Processing
Type 2 Diabetes Mellitus
Animal Models
Bacteria
Amino Acids
Glucose
Mutation
Proteins

Keywords

  • Clp protease
  • Diabetes
  • Host-pathogen interactions
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Jacquet, R., LaBauve, A. E., Akoolo, L., Patel, S., Alqarzaee, A. A., Fok Lung, T. W., ... Parker, D. (2019). Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice. Infection and immunity, 87(5), [e00163-19]. https://doi.org/10.1128/IAI.00163-19

Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice. / Jacquet, Rudy; LaBauve, Annette E.; Akoolo, Lavoisier; Patel, Shivani; Alqarzaee, Abdulelah A.; Fok Lung, Tania Wong; Poorey, Kunal; Stinear, Timothy P.; Thomas, Vinai C.; Meagher, Robert J.; Parker, Dane.

In: Infection and immunity, Vol. 87, No. 5, e00163-19, 01.05.2019.

Research output: Contribution to journalArticle

Jacquet, R, LaBauve, AE, Akoolo, L, Patel, S, Alqarzaee, AA, Fok Lung, TW, Poorey, K, Stinear, TP, Thomas, VC, Meagher, RJ & Parker, D 2019, 'Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice', Infection and immunity, vol. 87, no. 5, e00163-19. https://doi.org/10.1128/IAI.00163-19
Jacquet, Rudy ; LaBauve, Annette E. ; Akoolo, Lavoisier ; Patel, Shivani ; Alqarzaee, Abdulelah A. ; Fok Lung, Tania Wong ; Poorey, Kunal ; Stinear, Timothy P. ; Thomas, Vinai C. ; Meagher, Robert J. ; Parker, Dane. / Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice. In: Infection and immunity. 2019 ; Vol. 87, No. 5.
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