Effect of peptide and amino acid catabolism on the growth dynamic and colonization efficiency of Campylobacter jejuni

空肠弯曲杆菌是人类胃肠道感染的常见原因，人们对空肠弯曲菌在宿主体内高效生长所必需的生理要求知之甚少。我们感兴趣的是寻找能够使空肠弯曲菌在不同环境中存活的生长底物。空肠弯曲菌不能代谢碳水化合物，碳水化合物是许多共生和致病肠道细菌的主要能量来源。相反，产糖氨基酸似乎是空肠弯曲菌首选的碳和氮来源。由于肠道中含有丰富的多肽，我们推测空肠弯曲菌对这些多肽的分解代谢有助于其生长。通过定向突变，我们将破译特定的肽酶、肽转运体和氨基酸转运体对空肠弯曲菌生长的重要性。我们将通过使用不同的动物感染模型测试特定的突变株在体内的定植能力，进一步分析假设的空肠弯曲菌生长因子的意义。这些研究将通过对空肠弯曲菌体外培养过程中含有多肽的生长介质的代谢组学分析来确定哪些多肽可以被空肠弯曲菌利用来生长。随着这个项目的完成，我们不仅将发现空肠弯曲菌中可能作为潜在药物靶点的必要代谢途径，而且我们还将对病原体在感染过程中如何获取营养有更好的总体了解。

Campylobacter jejuni is a common cause of gastrointestinal infections in humans and little is known about the physiological requirements essential for C. jejuni to thrive efficiently in its hosts. We are interested in identifying growth substrates that allow C. jejuni to persist in its different environments. C. jejuni is unable to metabolize carbohydrates, the major energy source of many commensal and pathogenic intestinal bacteria. Instead, glucogenic amino acids seem to be the preferred source of carbon and nitrogen for C. jejuni. Because peptides are abundant in the intestine, we hypothesize that the catabolism of these peptides by C. jejuni contributes to its growth. With targeted mutagenesis we will decipher the importance of specific peptidases, peptide transporters and amino acid transporters for the growth of C. jejuni. We will further analyze the significance of putative growth factors of C. jejuni by testing specific mutants for their in vivo colonization capability using different animal models of infection. These studies will be complemented by metabolomic analyses of peptide-containing growth media during the cultivation of C. jejuni in vitro to identify which peptides that can be utilized by C. jejuni for growth. With completion of this project we will not only discover essential metabolic pathways in C. jejuni that could serve as potential drug targets, but we will also gain a better general understanding of how pathogens access nutrients during infection.