Genetic anaylsis of pediatric osteoarticular infections

Background: Pediatric osteoarticular infections are commonly caused by
Staphylococcus aureus. The contribution of S. aureus genomic variability
to pathogenesis of these infections is poorly described. 
Methods: We prospectively enrolled 47 children over 3 1/2 years from whom
S. aureus was isolated on culture---12 uninfected with skin colonization,
16 with skin abscesses, 19 with osteoarticular infections (four with
septic arthritis, three with acute osteomyelitis, six with acute
osteomyelitis and septic arthritis and six with chronic osteomyelitis).
Isolates underwent whole genome sequencing, with assessment for 254
virulence genes and any mutations as well as the creation of a
phylogenetic tree. Finally, isolates were compared for their ability to
form static biofilms and compared to the genetic analysis. Results: No
sequence types predominated amongst osteoarticular infections. Only genes
involved in the evasion of host immune defenses were more frequently
carried by isolates from osteoarticular infections than from skin
colonization (p=.02). Virulence gene mutations were only noted in 14 genes
(three regulating biofilm formation) when comparing isolates from subjects
with osteoarticular infections and those with skin colonization. Biofilm
results demonstrated large heterogeneity in the isolates’ capacity to form
static biofilms, with healthy control isolates producing more robust
biofilm formation. Conclusions: S. aureus causing osteoarticular
infections are genetically heterogeneous, and more frequently harbor genes
involved in immune evasion than less invasive isolates. However, virulence
gene carriage overall is similar with infrequent mutations, suggesting
that pathogenesis of S. aureus osteoarticular infections may be primarily
regulated at transcriptional and/or translational levels.