Abstract
The mechanisms or host factors involved in septic thrombus or vegetation formation
in Staphylococcus aureus-induced infective endocarditis (IE) are unclear. Using an experimental endocarditis
rat model, here we demonstrated that S. aureus HG001-induced vegetation was composed of bacterial floes encased in aggregated platelets
and surrounded by neutrophil extracellular traps (NETs). In vitro data demonstrated
that platelets contribute to both biofilm and NET formation. Prophylactic administration
of DNase I significantly reduced the size of vegetation induced by methicillin-resistant
S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains, even though MRSA and MSSA isolates express different biofilm phenotypes
and NET-induction abilities in the presence of platelets. Moreover, delivery of both
DNase I and daptomycin prophylactically and therapeutically produced synergistic effects
by reducing vegetation size and bacterial numbers on damaged valve tissues in MRSA-induced
IE. Together, these data suggest that NETs contribute to vegetation formation in S. aureus endocarditis and DNase I has the potential to control S. aureus-induced IE in the clinic.
Keywords
infective endocarditis - staphylococcus aureus - neutrophil extracellular traps -
platelets - DNase I
