Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom.
Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Elife. 2024 Aug 27;12:RP88971. doi: 10.7554/eLife.88971.
is a global public health concern due to the rising myriad of hypervirulent and multidrug-resistant clones both alarmingly associated with high mortality. The molecular mechanisms underpinning these recalcitrant infection, and how virulence is coupled with the emergence of lineages resistant to nearly all present-day clinically important antimicrobials, are unclear. In this study, we performed a genome-wide screen in ECL8, a member of the endemic K2-ST375 pathotype most often reported in Asia, to define genes essential for growth in a nutrient-rich laboratory medium (Luria-Bertani [LB] medium), human urine, and serum. Through transposon directed insertion-site sequencing (TraDIS), a total of 427 genes were identified as essential for growth on LB agar, whereas transposon insertions in 11 and 144 genes decreased fitness for growth in either urine or serum, respectively. These studies not only provide further knowledge on the genetics of this pathogen but also provide a strong impetus for discovering new antimicrobial targets to improve current therapeutic options for infections.
是一个全球性的公共卫生关注,由于不断出现的多种高毒性和多药耐药克隆体,这些克隆体与高死亡率惊人地相关。这些顽固的感染的分子机制,以及毒力如何与几乎所有目前临床上重要的抗菌药物耐药谱系的出现相关,尚不清楚。在这项研究中,我们对 ECL8 进行了全基因组筛选,ECL8 是地方性 K2-ST375 病原株的成员,该病原株最常报告于亚洲,以确定在营养丰富的实验室培养基(Luria-Bertani [LB] 培养基)、人尿和血清中生长所必需的基因。通过转座子定向插入位点测序(TraDIS),总共鉴定出 427 个基因对 LB 琼脂上的生长是必需的,而转座子插入 11 个和 144 个基因分别降低了在尿或血清中生长的适应性。这些研究不仅为该病原体的遗传学提供了更多的知识,而且为发现新的抗菌药物靶点以改善目前的治疗方案提供了强有力的动力。