Identification of potential key genetic factors in the long-term success of Shigella as pathogens
Identification of potential key genetic factors in the long-term success of Shigella as pathogens
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鉴定志贺氏菌作为病原体长期成功的潜在关键遗传因素
DOI：
10.1099/acmi.ac2020.po1043
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发表时间：
2020
影响因子：
--
通讯作者：
Bennett R
中科院分区：
文献类型：
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作者：
Bennett R
志贺氏菌属细菌是造成全球腹泻负担的主要因素，每年导致全球 10 万人死亡。此外，志贺氏菌的抗生素耐药性不断增加，而且缺乏获得许可的疫苗，导致世界卫生组织将志贺氏菌视为开发新抗生素的优先生物体。了解是什么推动了这种病原体的长期存在和成功，将有助于志贺氏菌病的全球管理，并可能确定与其他肠道细菌相关的目标。为了确定过去 100 年来志贺氏菌进化的关键遗传驱动因素，我们使用了历史上的 Murray 收集品；包括来自不同地理位置的数百种前抗生素时代（1917 – 1954）肠杆菌科细菌。我们对 Murray 菌种中 100 多个志贺菌分离株以及更现代的（即 1950 年代 - 2018 年）分离株的序列进行了全基因组关联研究，以识别与时间显着相关的遗传因素（SNP 和基因）作为连续变量。然后对 GWAS 命中（例如假定的抗性蛋白）进行变异、功能和表型分析，以检查它们在塑造志贺氏菌种群中的作用以及作为管理这种病原体的潜在目标的合理性。
Bacterial of the genusShigellaare a major contributor to the global diarrhoea burden causing 100,000 deaths per annum globally. Further to this, increasing antibiotic resistance inShigellaand the lack of a licenced vaccine has led WHO to recogniseShigellaas a priority organism for the development of new antibiotics. Understanding what drives the long-term persistence and success of this pathogen will thus aid the global management of shigellosis and may identify targets relevant to other enteric bacteria. To identify key genetic drivers of Shigella evolution over the past 100 years, we have used the historical Murray collection; comprising several hundred pre-antibiotic era (1917 – 1954) Enterobacteriaceae from diverse geographical locations. We employed genome-wide association studies to sequences from over 100Shigellaisolates from the Murray collection alongsidemore modern (i.e. 1950s – 2018) isolates to identify genetic factors (SNPs and genes) significantly associated with time as a continuous variable. GWAS hits (e.g. a putative resistance protein) then underwent variation, functional and phenotypic analysis to examine the plausibility of their role in shapingShigellapopulations and as potential targets for managing this pathogen.