Affiliation:
1. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, BC Children’s Hospital Research Institute and the University of British Columbia, Vancouver, BC V5Z 4H4, Canada
2. ARC Centre of Excellence for Synthetic Biology, School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, North Ryde, Sydney, NSW 2109, Australia
Abstract
Enteric bacterial pathogens pose significant threats to human health; however, the mechanisms by which they infect the mammalian gut in the face of daunting host defenses and an established microbiota remain poorly defined. For the attaching and effacing (A/E) bacterial family member and murine pathogen
Citrobacter rodentium
, its virulence strategy likely involves metabolic adaptation to the host’s intestinal luminal environment, as a necessary precursor to reach and infect the mucosal surface. Suspecting this adaptation involved the intestinal mucus layer, we found that
C. rodentium
was able to catabolize sialic acid, a monosaccharide derived from mucins, and utilize it as its sole carbon source for growth. Moreover,
C. rodentium
also sensed and displayed chemotactic activity toward sialic acid. These activities were abolished when the
nanT
gene, encoding a sialic acid transporter, was deleted (Δ
nanT
). Correspondingly, the Δ
nanT C. rodentium
strain was significantly impaired in its ability to colonize the murine intestine. Intriguingly, sialic acid was also found to induce the secretion of two autotransporter proteins, Pic and EspC, which possess mucinolytic and host-adherent properties. As a result, sialic acid enhanced the ability of
C. rodentium
to degrade intestinal mucus (through Pic), as well as to adhere to intestinal epithelial cells (through EspC). We thus demonstrate that sialic acid, a monosaccharide constituent of the intestinal mucus layer, functions as an important nutrient and a key signal for an A/E bacterial pathogen to escape the colonic lumen and directly infect its host’s intestinal mucosa.
Funder
Gouvernement du Canada | Canadian Institutes of Health Research
Crohn's and Colitis Canada
Publisher
Proceedings of the National Academy of Sciences
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献