Genomic characterization of Staphylococcus aureus isolates causing osteoarticular infections in otherwise healthy children

Abstract

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 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 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.

Surgical management of chronic osteomyelitis: Organisms, recurrence and treatment outcome

“…Newer technologies like novel antibiotic laden biomaterials are made available with a view to reducing this complication. Further additions to the armamentarium aiming at reduction of recurrence include: use of artificial intelligence for diagnostics, 20 predictive modelling for risk factors, 21 genomic characterisation for virulence and antibiotic resistance, 22 novel 3D printed customised implants 23 and aggressive, and combined osteo-plastic surgical strategies. 24 …”

Acute haematogenous osteomyelitis in the paediatric population: a current concepts review

“…AHOM can cause devastating destruction of the bone due to tissue necrosis, leading to late sequelae like chronic osteomyelitis (1.7%) 3 and pathological fractures 5,23,31,36 (Figure 6). Complications such as these are more common in children in LMICs.…”

“…[2][3][4]7,12,[16][17][18] Some studies have reported a higher median age of presentation of between 6.7 and 11.1 years. 5,8,14,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Males appear to be between 1.2 and 3.6 times more affected than females.…”

“…43,48 These factors could provide potential targets for immunotherapeutic agents and vaccines. 36 Panton-Valentine leukocidin (PVL) is a necrotising toxin seen in methicillin-sensitive S. aureus (MSSA) and methicillinresistant S. aureus (MRSA) bacteria, and is seen with increasing frequency. 7,11,17,40,69,70 This toxin targets white blood cells causing destruction and tissue necrosis.…”