title: YbcL of uropathogenic Escherichia coli suppresses transepithelial neutrophil migration.
abstract: Uropathogenic Escherichia coli (UPEC) strains suppress the acute inflammatory response in the urinary tract to ensure access to the intracellular uroepithelial niche that supports the propagation of infection. Our understanding of this initial cross talk between host and pathogen is incomplete. Here we report the identification of a previously uncharacterized periplasmic protein, YbcL, encoded by UPEC that contributes to immune modulation in the urinary tract by suppressing acute neutrophil migration. In contrast to wild-type UPEC, an isogenic strain lacking ybcL expression (UTI89 ΔybcL) failed to suppress transepithelial polymorphonuclear leukocyte (PMN) migration in vitro, a defect complemented by expressing ybcL episomally. YbcL homologs are present in many E. coli genomes; expression of the YbcL variant encoded by nonpathogenic E. coli K-12 strain MG1655 (YbcL(MG)) failed to complement the UTI89 ΔybcL defect, whereas expression of the UPEC YbcL variant (YbcL(UTI)) in MG1655 conferred the capacity for suppressing PMN migration. This phenotypic difference was due to a single amino acid difference (V78T) between the two YbcL homologs, and a majority of clinical UPEC strains examined were found to encode the suppressive YbcL variant. Purified YbcL(UTI) protein suppressed PMN migration in response to live or killed MG1655, and YbcL(UTI) was detected in the supernatant during UPEC infection of bladder epithelial cells or PMNs. Lastly, early PMN influx to murine bladder tissue was augmented upon in vivo infection with UTI89 ΔybcL compared with wild-type UPEC. Our findings demonstrate a role for UPEC YbcL in suppression of the innate immune response during urinary tract infection.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Lau
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Loughman
authors.forename: David A
authors.initials: DA
authors.lastname: Hunstad
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D002460:Cell Line; D003556:Cystitis / Q000276:immunology* / Q000382:microbiology; D004847:Epithelial Cells; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects / Q000276:immunology; D001743:Urinary Bladder; D014552:Urinary Tract Infections / Q000276:immunology* / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000472:pathogenicity*; D019459:Urothelium / Q000276:immunology
chemical_list: D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C432085:ybcL protein, E coli