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

Journal Article · · Infection and Immunity
DOI:https://doi.org/10.1128/IAI.00163-19· OSTI ID:1507413
 [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)

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.

Research Organization:
Sandia National Lab. (SNL-CA), Livermore, CA (United States)
Sponsoring Organization:
USDOE National Nuclear Security Administration (NNSA)
Grant/Contract Number:
AC04-94AL85000
OSTI ID:
1507413
Report Number(s):
SAND-2019-3398J; 673820
Journal Information:
Infection and Immunity, Vol. 87, Issue 5; ISSN 0019-9567
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 13 works
Citation information provided by
Web of Science

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