Metabolic and fitness determinants for in vitro growth and intestinal colonization of the bacterial pathogen Campylobacter jejuni

Campylobacter jejuni is one of the leading infectious causes of food-borne illness around the world. Its ability to persistently colonize the intestinal tract of a broad range of hosts, including food-producing animals, is central to its epidemiology since most infections are due to the consumption of contaminated food products. Using a highly saturated transposon insertion library combined with next-generation sequencing and a mouse model of infection, we have carried out a comprehensive genome-wide analysis of the fitness determinants for growth in vitro and in vivo of a highly pathogenic strain of C. jejuni. A comparison of the C. jejuni requirements to colonize the mouse intestine with those necessary to grow in different culture media in vitro, combined with isotopologue profiling and metabolic flow analysis, allowed us to identify its metabolic requirements to establish infection, including the ability to acquire certain nutrients, metabolize specific substrates, or maintain intracellular ion homeostasis. This comprehensive analysis has identified metabolic pathways that could provide the basis for the development of novel strategies to prevent C. jejuni colonization of food-producing animals or to treat human infections.空肠弯曲菌（Campylobacter jejuni）是全球范围内引发食源性感染的主要致病菌之一。其能够持续定殖包括食用动物在内的多种宿主的肠道，这一特性是其流行病学特征的核心，因为绝大多数人类感染均源于食用受污染的食品。本研究采用高饱和转座子插入文库结合二代测序技术，并利用感染小鼠模型，对高致病株空肠弯曲菌的体外及体内生长适应性决定因子开展了全基因组范围的系统性分析。通过对比空肠弯曲菌定殖小鼠肠道所需的条件与体外不同培养基中生长所需的条件，并结合同位素标记物谱分析与代谢流分析，我们得以明确其建立感染所需的代谢条件，包括获取特定营养物质、代谢特异性底物以及维持细胞内离子稳态的能力。本系统性分析鉴定出的代谢通路，可为开发预防食用动物空肠弯曲菌定殖或治疗人类感染的新型策略提供理论基础。