title: Escherichia coli global gene expression in urine from women with urinary tract infection.
abstract: Murine models of urinary tract infection (UTI) have provided substantial data identifying uropathogenic E. coli (UPEC) virulence factors and assessing their expression in vivo. However, it is unclear how gene expression in these animal models compares to UPEC gene expression during UTI in humans. To address this, we used a UPEC strain CFT073-specific microarray to measure global gene expression in eight E. coli isolates monitored directly from the urine of eight women presenting at a clinic with bacteriuria. The resulting gene expression profiles were compared to those of the same E. coli isolates cultured statically to exponential phase in pooled, sterilized human urine ex vivo. Known fitness factors, including iron acquisition and peptide transport systems, were highly expressed during human UTI and support a model in which UPEC replicates rapidly in vivo. While these findings were often consistent with previous data obtained from the murine UTI model, host-specific differences were observed. Most strikingly, expression of type 1 fimbrial genes, which are among the most highly expressed genes during murine experimental UTI and encode an essential virulence factor for this experimental model, was undetectable in six of the eight E. coli strains from women with UTI. Despite the lack of type 1 fimbrial expression in the urine samples, these E. coli isolates were generally capable of expressing type 1 fimbriae in vitro and highly upregulated fimA upon experimental murine infection. The findings presented here provide insight into the metabolic and pathogenic profile of UPEC in urine from women with UTI and represent the first transcriptome analysis for any pathogenic E. coli during a naturally occurring infection in humans.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Hagan
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Lloyd
authors.forename: David A
authors.initials: DA
authors.lastname: Rasko
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Faerber
authors.forename: Harry L T
authors.initials: HL
authors.lastname: Mobley
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D015153:Blotting, Western; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000235:genetics* / Q000382:microbiology / Q000652:urine; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000652:urine; D005260:Female; D020869:Gene Expression Profiling; D006384:Hemagglutination; D006801:Humans; D051379:Mice; D008808:Mice, Inbred CBA; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012329:RNA, Bacterial / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014552:Urinary Tract Infections / Q000235:genetics / Q000382:microbiology* / Q000652:urine; D037521:Virulence Factors / Q000235:genetics* / Q000652:urine; D055815:Young Adult
chemical_list: D015415:Biomarkers; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D037521:Virulence Factors