Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Wellcome Sanger Institute, Hinxton, UK.
Nat Commun. 2023 Mar 18;14(1):1530. doi: 10.1038/s41467-023-37200-w.
Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20-40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research.
即使在高收入国家的最佳复苏环境中，严重脓毒症和感染性休克的死亡率仍为 20-40%，而抗生素耐药性显著增加了这一死亡风险。为了开发一个参考数据集，以确定治疗干预的常见细菌靶标，我们应用了标准化的基因组、转录组、蛋白质组和代谢组学技术框架，对四种引起脓毒症的病原体的多个临床分离株进行了研究：大肠杆菌、肺炎克雷伯菌属复合种、金黄色葡萄球菌和化脓性链球菌。暴露于人血清中会产生一个脓毒症分子特征，其中包括脂肪酸和脂质生物合成和代谢的全面增加，这与细胞膜重塑和营养物质适应渗透保护有关。此外，还发现了跨细菌物种获取胆固醇的现象。这个详细的参考数据集已经作为一个开放资源建立，以支持发现和转化研究。
