Department of Infectious Diseases and Shenzhen Key Laboratory for Endogenous Infections, The 6th Affiliated Hospital of Shenzhen University Health Center, Shenzhen, Guangdong, China.
Department of Pharmacy Practice and Translational Research, University of Houston, Houston, Texas, USA.
Virulence. 2022 Dec;13(1):1920-1927. doi: 10.1080/21505594.2022.2132053.
has emerged as a common cause of bloodstream infections, which is associated with high mortality and long periods of hospitalization. To advance the medical care of our patients, the study was designed to identify microbial characteristics associated with poor clinical outcomes. A collection of 32 bloodstream isolates with diverse genetic backgrounds (as determined by multilocus sequence typing) was studied. These isolates were recovered by unique patients (18 males, 14 females; age range: 17 days to 87 years) between 2011 and 2018. A sequential screening approach (cross-referencing analyses using different endpoints) was used to identify isolates with the best correlation between bacterial virulence and clinical prognosis. Isolates associated with more rapid growth rate, shorter median survival time in pre-clinical infection models, and hospital mortality were selected as candidates for high virulence, while those with opposite characteristics were selected as controls with low virulence. Whole genome sequencing was undertaken in the most promising clinical isolates. We found five virulence genes (beta-hemolysin/cytolysin, Cpi-1a + Cpi-1 (SPI-1 like), enhanced entry proteins, FbpABC, Paa) and 1 secretory system (T6SS) only present in a highly virulent isolate (AB23), compared to a low virulence control isolate (AB6). These genetic elements could be associated with the poor prognosis of bacteraemia and further investigations are warranted.
已经成为血流感染的常见病因,与高死亡率和长时间住院有关。为了提高我们患者的医疗护理水平,本研究旨在确定与不良临床结局相关的微生物特征。研究收集了 32 株具有不同遗传背景(通过多位点序列分型确定)的血流分离株。这些分离株是在 2011 年至 2018 年间由独特的患者(18 名男性,14 名女性;年龄范围:17 天至 87 岁)分离得到的。采用顺序筛选方法(使用不同终点的交叉参照分析)来鉴定与细菌毒力和临床预后相关性最好的分离株。选择与更快的生长速度、临床前感染模型中较短的中位生存时间和医院死亡率相关的分离株作为高毒力的候选物,而选择具有相反特征的分离株作为低毒力的对照物。对最有前景的临床分离株进行了全基因组测序。我们发现了五个毒力基因(β-溶血素/细胞毒素、Cpi-1a+Cpi-1(SPI-1 样)、增强入侵蛋白、FbpABC、Paa)和一个分泌系统(T6SS),仅存在于一个高毒力分离株(AB23)中,而在一个低毒力对照分离株(AB6)中不存在。这些遗传元件可能与菌血症的不良预后有关,需要进一步研究。