ArticleInfection and immunity2016
Impact of sarA and Phenol-Soluble Modulins on the Pathogenesis of Osteomyelitis in Diverse Clinical Isolates of Staphylococcus aureus.
Article in Infection and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 56 citations in OpenAlex.
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- The major role ofVirulence · 2023Article
- New insight into the virulence and inflammatory response ofFrontiers in cellular and infection microbiology · 2023Article
- Horizontal transfer of probable chicken-pathogenicity chromosomal islands between Staphylococcus aureus and Staphylococcus agnetis.PloS one · 2023Article
- Microbiological aspects of osteomyelitis in veterinary medicine: drawing parallels to the infection in human medicine.The veterinary quarterly · 2022Review
- Fracture-related infection.Nature reviews. Disease primers · 2022Review
- Limiting protease production plays a key role in the pathogenesis of the divergent clinical isolates ofVirulence · 2021Article
- Contribution of Coagulase and Its Regulator SaeRS to Lethality of CA-MRSA 923 Bacteremia.Pathogens (Basel, Switzerland) · 2021Article
- Evaluation of a bone filler scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect.Scientific reports · 2021Article
- The Increased Accumulation of Staphylococcus aureus Virulence Factors Is Maximized in aInfection and immunity · 2021Article
- SarA plays a predominant role in controlling the production of extracellular proteases in the diverse clinical isolates ofVirulence · 2020Article
- The Crossroads between Infection and Bone Loss.Microorganisms · 2020Review
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10 authors at 2 institutions in 1 country.
Funding
Abstract
We used a murine model of acute, posttraumatic osteomyelitis to evaluate the virulence of two divergent Staphylococcus aureus clinical isolates (the USA300 strain LAC and the USA200 strain UAMS-1) and their isogenic sarA mutants. The results confirmed that both strains caused comparable degrees of osteolysis and reactive new bone formation in the acute phase of osteomyelitis. Conditioned medium (CM) from stationary-phase cultures of both strains was cytotoxic to cells of established cell lines (MC3TC-E1 and RAW 264.7 cells), primary murine calvarial osteoblasts, and bone marrow-derived osteoclasts. Both the cytotoxicity of CM and the reactive changes in bone were significantly reduced in the isogenic sarA mutants. These results confirm that sarA is required for the production and/or accumulation of extracellular virulence factors that limit osteoblast and osteoclast viability and that thereby promote bone destruction and reactive bone formation during the acute phase of S. aureus osteomyelitis. Proteomic analysis confirmed the reduced accumulation of multiple extracellular proteins in the LAC and UAMS-1 sarA mutants. Included among these were the alpha class of phenol-soluble modulins (PSMs), which were previously implicated as important determinants of osteoblast cytotoxicity and bone destruction and repair processes in osteomyelitis. Mutation of the corresponding operon reduced the cytotoxicity of CM from both UAMS-1 and LAC cultures for osteoblasts and osteoclasts. It also significantly reduced both reactive bone formation and cortical bone destruction by CM from LAC cultures. However, this was not true for CM from cultures of a UAMS-1 psmα mutant, thereby suggesting the involvement of additional virulence factors in such strains that remain to be identified.
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