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.

Blocking Yersiniabactin Import Attenuates Extraintestinal Pathogenic Escherichia coli in Cystitis and Pyelonephritis and Represents a Novel Target To Prevent Urinary Tract Infection

“…A recent study evaluating UPEC gene expression in elderly men and women with UTI found yersiniabactin system genes to be expressed in only 13 of 21 UPEC cystitis isolates (45). In contrast, a microarray-based study evaluating UPEC gene expression from women at a hospital urology clinic found fyuA to be highly expressed in seven of eight UPEC cystitis isolates (46). Potential variability in UPEC yersiniabactin system gene expression between UTI patient subpopulations will likely need to be taken into account during UPEC vaccine design.…”

Siderophore vaccine conjugates protect against uropathogenicEscherichia coliurinary tract infection

“…This report highlights the untapped resource of bacteria-specific small molecules as potential vaccine antigens and provides a proof of principle for incorporating these compounds into multicomponent vaccines for the prevention of bacterial infections. transcriptomic, and proteomic studies that have also identified iron acquisition systems as prime anti-UTI targets (21)(22)(23)(24)(25)(26)(27).…”

Uropathogenic enterobacteria use the yersiniabactin metallophore system to acquire nickel

“…Prominent among these is the Yersinia high pathogenicity island (HPI), which encodes the biosynthetic machinery to make the specialized metabolites yersiniabactin (Ybt) and escherichelin (2). Direct mass spectrometric detection of urinary Ybt in UTI patients, serological markers, transcriptional signatures, and experimental infection models all indicate active expression of Yersinia HPI proteins during UTI pathogenesis (3)(4)(5)(6)(7).…”