Exploiting Correlations between Protein Abundance and the Functional Status of saeRS and sarA To Identify Virulence Factors of Potential Importance in the Pathogenesis of Staphylococcus aureus Osteomyelitis
| Autor: | Alan J. Tackett, Rick D. Edmondson, Charity L. Washam, Samuel G. Mackintosh, Mark S. Smeltzer, Aura M. Ramirez, Karen E. Beenken, Horace J. Spencer, Stephanie D. Byrum |
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| Rok vydání: | 2019 |
| Předmět: |
Proteomics
0301 basic medicine Staphylococcus aureus Virulence Factors medicine.medical_treatment 030106 microbiology Virulence Biology medicine.disease_cause Article biofilm Microbiology Pathogenesis Mice 03 medical and health sciences Bacterial Proteins medicine Animals Protease Strain (chemistry) Osteomyelitis Biofilm osteomyelitis protease Gene Expression Regulation Bacterial Staphylococcal Infections medicine.disease Mice Inbred C57BL 030104 developmental biology Infectious Diseases Biofilms Mutation Trans-Activators Female Protein Kinases |
| Zdroj: | ACS Infectious Diseases |
| ISSN: | 2373-8227 |
| Popis: | We used a murine model of postsurgical osteomyelitis (OM) to evaluate the relative virulence of the Staphylococcus aureus strain LAC and five isogenic variants that differ in the functional status of saeRS and sarA relative to each other. LAC and a variant in which saeRS activity is increased (saeC) were comparably virulent to each other, while ΔsaeRS, ΔsarA, ΔsaeRS/ΔsarA, and saeC/ΔsarA mutants were all attenuated to a comparable degree. Phenotypic comparisons including a mass-based proteomics approach that allowed us to assess the number and abundance of full-length proteins suggested that mutation of saeRS attenuates virulence in our OM model owing primarily to the decreased production of S. aureus virulence factors, while mutation of sarA does so owing to protease-mediated degradation of these same virulence factors. This was confirmed by demonstrating that eliminating protease production restored virulence to a greater extent in a LAC sarA mutant than in the isogenic saeRS mutant. Irrespective of the mechanism involved, mutation of saeRS or sarA was shown to result in reduced accumulation of virulence factors of potential importance. Thus, using our proteomics approach we correlated the abundance of specific proteins with virulence in these six strains and identified 14 proteins that were present in a significantly increased amount (log2 ≥ 5.0) in both virulent strains by comparison to all four attenuated strains. We examined biofilm formation and virulence in our OM model using a LAC mutant unable to produce one of these 14 proteins, specifically staphylocoagulase. The results confirmed that mutation of coa limits biofilm formation and, to a lesser extent, virulence in our OM model, although in both cases the limitation was reduced by comparison to the isogenic sarA mutant. |
| Databáze: | OpenAIRE |
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