title: Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration.
abstract: Citrobacter rodentium uses a type III secretion system (T3SS) to induce colonic crypt hyperplasia in mice, thereby gaining an edge during its competition with the gut microbiota through an unknown mechanism. Here, we show that by triggering colonic crypt hyperplasia, the C. rodentium T3SS induced an excessive expansion of undifferentiated Ki67-positive epithelial cells, which increased oxygenation of the mucosal surface and drove an aerobic C. rodentium expansion in the colon. Treatment of mice with the γ-secretase inhibitor dibenzazepine to diminish Notch-driven colonic crypt hyperplasia curtailed the fitness advantage conferred by aerobic respiration during C. rodentium infection. We conclude that C. rodentium uses its T3SS to induce histopathological lesions that generate an intestinal microenvironment in which growth of the pathogen is fueled by aerobic respiration.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lopez
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA, USA.
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Miller
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA, USA.
authors.forename: Fabian
authors.initials: F
authors.lastname: Rivera-Chávez
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Velazquez
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA, USA.
authors.forename: Mariana X
authors.initials: MX
authors.lastname: Byndloss
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Chávez-Arroyo
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Lokken
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA, USA.
authors.forename: Renée M
authors.initials: RM
authors.lastname: Tsolis
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, USA.
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Winter
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA, USA. ajbaumler@ucdavis.edu.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
mesh_terms: D000332:Aerobiosis; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D044082:Citrobacter rodentium / Q000235:genetics / Q000472:pathogenicity*; D003092:Colitis / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology*; D003106:Colon / Q000382:microbiology / Q000473:pathology; D003580:Cytochromes / Q000235:genetics / Q000502:physiology; D003984:Dibenzazepines / Q000627:therapeutic use; D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000502:physiology; D004756:Enterobacteriaceae Infections / Q000382:microbiology* / Q000473:pathology*; D017353:Gene Deletion; D006965:Hyperplasia / Q000382:microbiology / Q000473:pathology; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009566:Nitrates / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D003580:Cytochromes; D003984:Dibenzazepines; D045222:Electron Transport Chain Complex Proteins; D019394:Ki-67 Antigen; D009566:Nitrates; D051880:Receptors, Notch; D037521:Virulence Factors; D010088:Oxidoreductases; D053829:Amyloid Precursor Protein Secretases; C527817:dibenzazepine