Free Margaret, Soper Nicole, Slaughter James C, Feder Andries, Bianco Colleen, Moustafa Ahmed M, Planet Paul, Creech C Buddy, Thomsen Isaac
Department of Pediatrics, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
Vanderbilt Vaccine Research Program, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
PLoS One. 2025 Jul 31;20(7):e0326353. doi: 10.1371/journal.pone.0326353. eCollection 2025.
Invasive Staphylococcus aureus infections cause high morbidity and mortality in children and adults. With rising antimicrobial resistance, optimal prevention strategies and novel therapeutics are needed. As an effective vaccine remains elusive, characterization of invasive isolates over time is required to identify determinants of invasive infection.
S. aureus isolates recovered from children with invasive infection and those with colonization were obtained. Isolates were examined by whole genome sequencing to evaluate gene repertoire, sequence type, clonal complex, and phylogenetic characterization, and isolate characteristics were correlated to clinical data.
118 children with invasive S. aureus infections were enrolled; 56% of infections were caused by methicillin-susceptible S. aureus (MSSA). Methicillin-resistance (MRSA) was associated with increased inflammation, though clinical outcomes of MRSA vs MSSA did not differ. Colonization isolates exhibited higher sequence type diversity than invasive isolates. Nine distinct clonal complexes (CC) were identified among all isolates; CC8 and CC5 were associated with higher clinical severity scores. Accessory gene regulator locus type 1, Panton-Valentine Leukocidin, and arginine catabolic mobile element declined over time. Staphylokinase and leukocidin ED were associated with invasive infection, while enterotoxin B was more frequent in colonizing isolates.
We observed a significant expansion in sequence type diversity among invasive clinical isolates over 12 years with the emergence of newly invasive clones in recent years. The presence of staphylokinase and LukED were associated with invasive infection over time. These findings provide insights into the pathogenesis of invasive S. aureus and may provide putative targets for immunologic approaches to prevention.
侵袭性金黄色葡萄球菌感染在儿童和成人中可导致高发病率和死亡率。随着抗菌药物耐药性的不断上升，需要最佳的预防策略和新型治疗方法。由于有效的疫苗仍难以实现，因此需要对侵袭性分离株进行长期特征分析，以确定侵袭性感染的决定因素。
获取从侵袭性感染儿童和定植儿童中分离出的金黄色葡萄球菌。通过全基因组测序对分离株进行检测，以评估基因库、序列类型、克隆复合体和系统发育特征，并将分离株特征与临床数据相关联。
纳入118例侵袭性金黄色葡萄球菌感染儿童；56%的感染由甲氧西林敏感金黄色葡萄球菌（MSSA）引起。耐甲氧西林（MRSA）与炎症增加相关，尽管MRSA与MSSA的临床结局并无差异。定植分离株的序列类型多样性高于侵袭性分离株。在所有分离株中鉴定出9种不同的克隆复合体（CC）；CC8和CC5与更高的临床严重程度评分相关。辅助基因调节位点类型1、杀白细胞素和精氨酸分解代谢移动元件随时间下降。葡萄球菌激酶和杀白细胞素ED与侵袭性感染相关，而定植分离株中肠毒素B更为常见。
我们观察到12年间侵袭性临床分离株的序列类型多样性显著增加，近年来出现了新的侵袭性克隆。随着时间的推移，葡萄球菌激酶和LukED的存在与侵袭性感染相关。这些发现为侵袭性金黄色葡萄球菌的发病机制提供了见解，并可能为预防的免疫方法提供假定靶点。
