The role of peptide catabolism on the colonization and growth dynamics of Campylobacter jejuni

空肠弯曲杆菌（Campylobacter jejuni）是人类胃肠道感染的常见原因，但对于空肠弯曲杆菌在宿主体内有效繁殖的生理要求知之甚少。我们感兴趣的是确定生长基质，使空肠梭菌在不同的环境中持续存在。空肠梭菌不能代谢碳水化合物，而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，糖原氨基酸似乎是空肠梭菌碳和氮的首选来源。由于肠内多肽丰富，我们假设空肠梭菌对这些多肽的分解代谢有助于其生长。通过靶向诱变，我们将破译特定肽酶、肽转运体和氨基酸转运体对空肠梭菌生长的重要性。我们将通过使用不同的感染动物模型测试特定突变体的体内定植能力，进一步分析推测的空肠梭菌生长因子的意义。这些研究将通过体外培养空肠梭菌过程中含肽生长培养基的代谢组学分析来补充，以确定哪些肽可以被空肠梭菌利用。随着这个项目的完成，我们不仅将发现空肠梭菌的基本代谢途径，可以作为潜在的药物靶点，而且我们也将更好地了解病原体在感染过程中如何获取营养。

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.