Phenol-Soluble Modulins Contribute to Early Sepsis Dissemination Not Late Local USA300-Osteomyelitis Severity in Rabbits.
PLoS One
; 11(6): e0157133, 2016.
Article
em En
| MEDLINE
| ID: mdl-27275944
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 α-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 ANDMETHODS:
We compared the outcomes of experimental rabbit osteomyelitises induced with pvl+hla+psms+ LAC WT and its isogenic Δpsm derivatives (LAC Δpsmα and LAC Δpsmαßhld) 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 Δpsm derivatives (Kaplan-Meier curves, P = .06). Non-survivors' bone LAC-Δpsmα (6.9 log10 CFUs/g of bone, P = .04) or -Δpsmαßhld (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 Δpsmαßhld CFUs were significantly lower than LAC WT (P = .04). LAC Δpsmα, Δpsmαßhld 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 Δpsmα- and Δpsmαßhld-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteomielite
/
Infecções Estafilocócicas
/
Toxinas Bacterianas
/
Sepse
/
Staphylococcus aureus Resistente à Meticilina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
França