{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["11(6)"],"submitter":["Davido B"],"pubmed_abstract":["INTRODUCTION:In bone and joint infections (BJIs), bacterial toxins are major virulence factors: Panton-Valentine leukocidin (PVL) expression leads to severe local damage, including bone distortion and abscesses, while ?-hemolysin (Hla) production is associated with severe sepsis-related mortality. Recently, other toxins, namely phenol-soluble modulins (PSMs) expressed by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA300 (LAC WT) were shown to have ex vivo intracellular cytotoxic activity after S. aureus invasion of osteoblasts, but their in vivo contribution in a relatively PVL-sensitive osteomyelitis model remains poorly elucidated. MATERIALS AND METHODS:We compared the outcomes of experimental rabbit osteomyelitises induced with pvl+hla+psms+ LAC WT and its isogenic ?psm derivatives (LAC ?psm? and LAC ?psm??hld) using an inoculum of 3 × 108 CFUs. Mortality, hematogenous spread (blood culture, spleen and kidney), lung and bone involvements were assessed in two groups (non-survivors of severe sepsis and survivors sacrificed on day (D) 14). RESULTS:Severe sepsis-related mortality tended to be lower for ?psm derivatives (Kaplan-Meier curves, P = .06). Non-survivors' bone LAC-?psm? (6.9 log10 CFUs/g of bone, P = .04) or -?psm??hld (6.86 log10 CFUs/g of bone, P = .014) densities were significantly higher than LAC WT (6.43 log10 CFUs/g of bone). Conversely, lung ?psm??hld CFUs were significantly lower than LAC WT (P = .04). LAC ?psm?, ?psm??hld and WT induced similar bone damage in D14 survivors, with comparable bacterial densities (respectively: 5.89, 5.91, and 6.15 log10 CFUs/g of bone). Meanwhile, pulmonary histological scores of inflammation were significantly higher for LAC ?psm?- and ?psm??hld-infected rabbits compared to LAC WT (P = .04 and .01, respectively) but with comparable lung bacterial densities. CONCLUSION:Our experimental results showed that deactivating PSM peptides significantly limited bacterial dissemination from bone during the early phase of infection, but did not affect local severity of USA300 rabbit osteomyelitis."],"journal":["PloS one"],"pagination":["e0157133"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4898696"],"repository":["biostudies-literature"],"pubmed_title":["Phenol-Soluble Modulins Contribute to Early Sepsis Dissemination Not Late Local USA300-Osteomyelitis Severity in Rabbits."],"pmcid":["PMC4898696"],"pubmed_authors":["Danel C","Couzon F","Cremieux AC","Davido B","Saleh-Mghir A","Rasigade JP","Laurent F","Vandenesch F","Gatin L"],"additional_accession":[]},"is_claimable":false,"name":"Phenol-Soluble Modulins Contribute to Early Sepsis Dissemination Not Late Local USA300-Osteomyelitis Severity in Rabbits.","description":"INTRODUCTION:In bone and joint infections (BJIs), bacterial toxins are major virulence factors: Panton-Valentine leukocidin (PVL) expression leads to severe local damage, including bone distortion and abscesses, while ?-hemolysin (Hla) production is associated with severe sepsis-related mortality. Recently, other toxins, namely phenol-soluble modulins (PSMs) expressed by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA300 (LAC WT) were shown to have ex vivo intracellular cytotoxic activity after S. aureus invasion of osteoblasts, but their in vivo contribution in a relatively PVL-sensitive osteomyelitis model remains poorly elucidated. MATERIALS AND METHODS:We compared the outcomes of experimental rabbit osteomyelitises induced with pvl+hla+psms+ LAC WT and its isogenic ?psm derivatives (LAC ?psm? and LAC ?psm??hld) using an inoculum of 3 × 108 CFUs. Mortality, hematogenous spread (blood culture, spleen and kidney), lung and bone involvements were assessed in two groups (non-survivors of severe sepsis and survivors sacrificed on day (D) 14). RESULTS:Severe sepsis-related mortality tended to be lower for ?psm derivatives (Kaplan-Meier curves, P = .06). Non-survivors' bone LAC-?psm? (6.9 log10 CFUs/g of bone, P = .04) or -?psm??hld (6.86 log10 CFUs/g of bone, P = .014) densities were significantly higher than LAC WT (6.43 log10 CFUs/g of bone). Conversely, lung ?psm??hld CFUs were significantly lower than LAC WT (P = .04). LAC ?psm?, ?psm??hld and WT induced similar bone damage in D14 survivors, with comparable bacterial densities (respectively: 5.89, 5.91, and 6.15 log10 CFUs/g of bone). Meanwhile, pulmonary histological scores of inflammation were significantly higher for LAC ?psm?- and ?psm??hld-infected rabbits compared to LAC WT (P = .04 and .01, respectively) but with comparable lung bacterial densities. CONCLUSION:Our experimental results showed that deactivating PSM peptides significantly limited bacterial dissemination from bone during the early phase of infection, but did not affect local severity of USA300 rabbit osteomyelitis.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016","modification":"2021-02-19T08:11:07Z","creation":"2019-03-26T22:53:56Z"},"accession":"S-EPMC4898696","cross_references":{"pubmed":["27275944"],"doi":["10.1371/journal.pone.0157133"]}}