title: The Rhomboid Protease GlpG Promotes the Persistence of Extraintestinal Pathogenic Escherichia coli within the Gut.
abstract: Extraintestinal pathogenicEscherichia coli(ExPEC) strains are typically benign within the mammalian gut but can disperse to extraintestinal sites to cause diseases like urinary tract infections and sepsis. As occupation of the intestinal tract is often a prerequisite for ExPEC-mediated pathogenesis, we set out to understand how ExPEC colonizes this niche. A screen using transposon sequencing (Tn-seq) was performed to search for genes within ExPEC isolate F11 that are important for growth in intestinal mucus, which is thought to be a major source of nutrients forE. coliin the gut. Multiple genes that contribute to ExPEC fitness in mucus broth were identified, with genes that are directly or indirectly associated with fatty acid beta-oxidation pathways being especially important. One of the identified mucus-specific fitness genes encodes the rhomboid protease GlpG.In vitro, we found that the disruption ofglpGhad polar effects on the downstream geneglpR, which encodes a transcriptional repressor of factors that catalyze glycerol degradation. Mutation of eitherglpGorglpRimpaired ExPEC growth in mucus and on plates containing the long-chain fatty acid oleate as the sole carbon source. In contrast, in a mouse gut colonization model in which the natural microbiota is unperturbed, the disruption ofglpGbut notglpRsignificantly reduced ExPEC survival. This work reveals a novel biological role for a rhomboid protease and highlights new avenues for defining mechanisms by which ExPEC strains colonize the mammalian gastrointestinal tract.
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Colin W
authors.initials: CW
authors.lastname: Russell
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Richards
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Chang
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, Utah, USA mulvey@path.utah.edu.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Mulvey
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D010450:Endopeptidases / Q000235:genetics*; D004927:Escherichia coli Infections / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics*; D000072282:Extraintestinal Pathogenic Escherichia coli / Q000201:enzymology / Q000235:genetics*; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D056084:Genetic Fitness; D007413:Intestinal Mucosa / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics; D018805:Sepsis / Q000382:microbiology
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C102898:GlpG protein, E coli; C101651:GlpR protein, E coli; D008565:Membrane Proteins; D012097:Repressor Proteins; D010450:Endopeptidases
keywords: ExPEC; UPEC; beta-oxidation; fatty acids; glycerol degradation; gut; intestinal; mucus; urinary tract infection; uropathogenic