Department of Pediatrics, The University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America.
Department of Internal Medicine, The University of New Mexico School of Medicine, Center for Global Health, Albuquerque, New Mexico, United States of America.
PLoS One. 2022 Aug 29;17(8):e0272425. doi: 10.1371/journal.pone.0272425. eCollection 2022.
Pediatric osteoarticular infections are commonly caused by Staphylococcus aureus. The contribution of S. aureus genomic variability to pathogenesis of these infections is poorly described.
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.
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.
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.
小儿骨关节炎感染通常由金黄色葡萄球菌引起。金黄色葡萄球菌基因组变异对这些感染发病机制的影响描述甚少。
我们前瞻性地招募了 47 名 3 岁半以上的儿童,从他们身上分离出金黄色葡萄球菌,其中 12 名未感染皮肤定植,16 名患有皮肤脓肿,19 名患有骨关节炎感染(4 名患有化脓性关节炎,3 名患有急性骨髓炎,6 名患有急性骨髓炎和化脓性关节炎,6 名患有慢性骨髓炎)。对分离株进行全基因组测序,评估 254 种毒力基因和任何突变,并构建系统发育树。最后,比较分离株形成静态生物膜的能力,并与遗传分析进行比较。
在骨关节炎感染中没有优势序列类型。只有参与逃避宿主免疫防御的基因,在骨关节炎感染分离株中比在皮肤定植分离株中携带更为频繁(p =.02)。在比较骨关节炎感染和皮肤定植分离株时,仅在 14 个基因(三个调节生物膜形成的基因)中发现了毒力基因突变。生物膜结果表明,分离株形成静态生物膜的能力存在很大的异质性,健康对照分离株产生更强大的生物膜形成能力。
引起骨关节炎感染的金黄色葡萄球菌在遗传上是异质的,并且比侵袭性较小的分离株更频繁地携带参与免疫逃避的基因。然而,总的来说,毒力基因的携带情况相似,突变频率较低,这表明金黄色葡萄球菌骨关节炎感染的发病机制可能主要受转录和/或翻译水平的调节。