TY - JOUR
T1 - Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice
AU - Jacquet, Rudy
AU - LaBauve, Annette E.
AU - Akoolo, Lavoisier
AU - Patel, Shivani
AU - Alqarzaee, Abdulelah A.
AU - Fok Lung, Tania Wong
AU - Poorey, Kunal
AU - Stinear, Timothy P.
AU - Thomas, Vinai C.
AU - Meagher, Robert J.
AU - Parker, Dane
N1 - Publisher Copyright:
© 2019 American Society for Microbiology. All Rights Reserved.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
KW - Clp protease
KW - Diabetes
KW - Host-pathogen interactions
KW - Staphylococcus aureus
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U2 - 10.1128/IAI.00163-19
DO - 10.1128/IAI.00163-19
M3 - Article
C2 - 30833333
AN - SCOPUS:85065047169
SN - 0019-9567
VL - 87
JO - Infection and immunity
JF - Infection and immunity
IS - 5
M1 - e00163-19
ER -