Abstract

Uropathogenic Escherichia coli (UPEC) adhere to cells in the human urinary tract via type 1 pili that undergo phase variation where a 314-bp fimS DNA element flips between Phase-ON and Phase-OFF orientations through two site-specific recombinases, FimB and FimE. Three fim-lux operon transcriptional fusions were created and moved into the clinical UPEC isolate NU149 to determine their temporal regulation in UPEC growing in the urinary tract. Within murine urinary tracts, the UPEC strains demonstrated elevated transcription of fimA and fimB early in the infection, but lower transcription by the fifth day in murine kidneys. In contrast, fimE transcription was much lower than either fimA or fimB early, increased markedly at 24 h after inoculation, and then dropped five days after inoculation. Positioning of fimS was primarily in the Phase-ON position over the time span in UPEC infected bladders, whereas in UPEC infected murine kidneys the Phase-OFF orientation was favored by the fifth day after inoculation. Hemagglutination titers with guinea pig erythrocytes remained constant in UPEC growing in infected murine bladders but fell substantially in UPEC infected kidneys over time. Our results show temporal in vivo regulation of fim gene expression in different environmental niches when UPEC infects the murine urinary tract.

Highlights

  • Urinary tract infections (UTIs) remain one of the most common infections of humans in the United States

  • More than 80% of all UTIs are due to uropathogenic Escherichia coli (UPEC), causing substantial morbidity and mortality, from the risk of sepsis during pyelonephritis [2]

  • We have demonstrated that the fimA, fimB, and fimE genes were differentially regulated in E. coli colonizing the bladder versus the kidney

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Summary

Introduction

Urinary tract infections (UTIs) remain one of the most common infections of humans in the United States. 10.5 million office visits are due to UTIs annually, resulting in over 100,000 hospitalizations and an estimated cost of $3.5 billion per year [1,2,3]. More than 80% of all UTIs are due to uropathogenic Escherichia coli (UPEC), causing substantial morbidity and mortality, from the risk of sepsis during pyelonephritis [2]. The ability to bind to uroepithelial cells lining the human urinary tract is generally considered one of the first steps in UPEC initiated UTIs. Type 1 pili facilitate this binding to epithelial cells in the bladder, lungs, intestine, and buccal cells; proximal tubular cells of the kidney; and various inflammatory cells [4,5,6]. Following adherence of the UPEC cells, bacterial invasion and persistence in target host cells due to the type 1 pili expressed by UPEC can occur [4, 7, 8]

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