Genetic anaylsis of pediatric osteoarticular infections

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.