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

Abstract

Staphylococcus aureus is a major human pathogen of the skin. The global burden of diabetes is high, with S. aureus 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 genes associated with translation, posttranslational modification and chaperones, and reductions in 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 clpXmore » were significantly attenuated and remained attenuation in both normal and diabetic mice. As a result, our data suggests that the diabetic environment also causes changes to occur in invading pathogens and one of these virulence determinants is the Clp protease system.« less

Authors:
 [1];  [2];  [3];  [1];  [4];  [1];  [5];  [6]; ORCiD logo [4];  [2];  [7]
  1. Columbia Univ., New York, NY (United States)
  2. Sandia National Lab. (SNL-CA), Livermore, CA (United States)
  3. Rutgers New Jersey Medical School, Newark, NJ (United States)
  4. Univ. of Nebraska Medical Center, Omaha, NE (United States)
  5. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
  6. Univ. of Melbourne, Melbourne, VIC (Australia)
  7. Columbia Univ., New York, NY (United States); Rutgers New Jersey Medical School, Newark, NJ (United States)
Publication Date:
Research Org.:
Sandia National Lab. (SNL-CA), Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1507413
Report Number(s):
SAND-2019-3398J
Journal ID: ISSN 0019-9567; 673820
Grant/Contract Number:  
AC04-94AL85000
Resource Type:
Accepted Manuscript
Journal Name:
Infection and Immunity
Additional Journal Information:
Journal Name: Infection and Immunity; Journal ID: ISSN 0019-9567
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Jacquet, Rudy, LaBauve, Annette E., Akoolo, Lavoisier, Patel, Shivani, Alqarzaee, Abdulelah A., Wong Fok Lung, Tania, Poorey, Kunal, Stinear, Timothy P., Thomas, Vinai C., Meagher, Robert, and Parker, Dane. Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice. United States: N. p., 2019. Web. doi:10.1128/IAI.00163-19.
Jacquet, Rudy, LaBauve, Annette E., Akoolo, Lavoisier, Patel, Shivani, Alqarzaee, Abdulelah A., Wong Fok Lung, Tania, Poorey, Kunal, Stinear, Timothy P., Thomas, Vinai C., Meagher, Robert, & Parker, Dane. Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice. United States. doi:10.1128/IAI.00163-19.
Jacquet, Rudy, LaBauve, Annette E., Akoolo, Lavoisier, Patel, Shivani, Alqarzaee, Abdulelah A., Wong Fok Lung, Tania, Poorey, Kunal, Stinear, Timothy P., Thomas, Vinai C., Meagher, Robert, and Parker, Dane. Mon . "Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice". United States. doi:10.1128/IAI.00163-19.
@article{osti_1507413,
title = {Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice},
author = {Jacquet, Rudy and LaBauve, Annette E. and Akoolo, Lavoisier and Patel, Shivani and Alqarzaee, Abdulelah A. and Wong Fok Lung, Tania and Poorey, Kunal and Stinear, Timothy P. and Thomas, Vinai C. and Meagher, Robert and Parker, Dane},
abstractNote = {Staphylococcus aureus is a major human pathogen of the skin. The global burden of diabetes is high, with S. aureus 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 genes associated with translation, posttranslational modification and chaperones, and reductions in 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 attenuation in both normal and diabetic mice. As a result, our data suggests that the diabetic environment also causes changes to occur in invading pathogens and one of these virulence determinants is the Clp protease system.},
doi = {10.1128/IAI.00163-19},
journal = {Infection and Immunity},
number = ,
volume = ,
place = {United States},
year = {2019},
month = {3}
}

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This content will become publicly available on March 4, 2020
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