Abstract
Elucidating how resident enteric bacteria interact with their hosts to promote health or inflammation is of central importance to diarrheal and inflammatory bowel diseases across species. Here, we integrated the microbial and chemical microenvironment of a patient’s ileal mucosa with their clinical phenotype and genotype to identify factors favoring the growth and virulence of adherent and invasive E. coli (AIEC) linked to Crohn’s disease. We determined that the ileal niche of AIEC was characterized by inflammation, dysbiosis, coculture of Enterococcus, and oxidative stress. We discovered that mucosal metabolites supported general growth of ileal E. coli, with a selective effect of ethanolamine on AIEC that was augmented by cometabolism of ileitis-associated amino acids and glutathione and by symbiosis-associated fucose. This metabolic plasticity was facilitated by the eut and pdu microcompartments, amino acid metabolism, γ-glutamyl-cycle, and pleiotropic stress responses. We linked metabolism to virulence and found that ethanolamine and glutamine enhanced AIEC motility, infectivity, and proinflammatory responses in vitro. We connected use of ethanolamine to intestinal inflammation and L-fuculose phosphate aldolase (fucA) to symbiosis in AIEC monoassociated IL10–/– mice. Collectively, we established that AIEC were pathoadapted to utilize mucosal metabolites associated with health and inflammation for growth and virulence, enabling the transition from symbiont to pathogen in a susceptible host.
Authors
Shiying Zhang, Xochitl Morgan, Belgin Dogan, Francois-Pierre Martin, Suzy Strickler, Akihiko Oka, Jeremy Herzog, Bo Liu, Scot E. Dowd, Curtis Huttenhower, Matthieu Pichaud, Esra I. Dogan, Jack Satsangi, Randy Longman, Rhonda Yantiss, Lukas A. Mueller, Ellen J. Scherl, R. Balfour Sartor, Kenneth W. Simpson
Figure 5
Cometabolism of amino acids modulates AIEC growth on ethanolamine, fucose, and glycerol, with GSH augmenting growth on ethanolamine.
