Metabolic and fitness determinants for in vitro growth and intestinal colonization of the bacterial pathogen Campylobacter jejuni.
Metabolic and fitness determinants for in vitro growth and intestinal colonization of the bacterial pathogen Campylobacter jejuni.
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DOI：
10.1371/journal.pbio.2001390
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发表时间：
2017-05
期刊：
影响因子：
9.8
通讯作者：
Hofreuter D
中科院分区：
文献类型：
--
作者：
Gao B;Vorwerk H;Huber C;Lara-Tejero M;Mohr J;Goodman AL;Eisenreich W;Galán JE;Hofreuter D
空肠弯曲菌是世界各地食源性疾病的主要感染原因之一。它能够在包括食用动物在内的广泛宿主的肠道中持续定殖，这是其流行病学的核心，因为大多数感染是由于食用受污染的食品造成的。利用高度饱和的转座子插入文库结合新一代测序和小鼠感染模型，我们对空肠弯曲菌高致病性菌株体外和体内生长的适应性决定因素进行了全面的全基因组分析。将空肠弯曲菌在小鼠肠道定植的要求与在体外不同培养基中生长所需的要求进行比较，结合同位素谱分析和代谢流分析，使我们能够确定其建立感染的代谢要求，包括获取某些营养物质、代谢特定底物或维持细胞内离子稳态的能力。这项综合分析确定了代谢途径，可以为制定新策略奠定基础，以防止空肠弯曲菌在食用动物中定植或治疗人类感染。越来越多的证据表明，除了毒素、粘附素或入侵素等典型毒力因子外，细菌病原体还利用特定的代谢特征在宿主体内定植和增殖，这一概念越来越多地被称为“营养毒力”。我们使用转座子插入诱变结合下一代测序、小鼠感染模型、同位素谱分析和代谢流分析，全面了解空肠弯曲菌肠道定植的代谢需求，空肠弯曲菌是工业化国家食源性胃肠炎的主要原因。该信息可以为控制空肠弯曲菌在食用动物或人类宿主中的定殖提供基础。
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. There is accumulating evidence that in addition to canonical virulence factors such as toxins, adhesins, or invasins, bacterial pathogens utilize specific metabolic traits to colonize and proliferate within their hosts, a concept that is increasingly referred to as “nutritional virulence”. We have used transposon insertion mutagenesis combined with next-generation sequencing, a mouse model of infection, isotopologue profiling, and metabolic flow analysis to obtain a comprehensive view of the metabolic requirements for the intestinal colonization of C. jejuni, a leading cause of food-borne gastroenteritis in industrialized countries. This information could provide the basis to control C. jejuni colonization of food-producing animals or the human host.