Intimate Attachment of Escherichia coli O157:H7 to Urinary Bladder Epithelium in the Gnotobiotic Piglet Model.

Rodney A Moxley,Tom W Bargar,Diane R Baker,David H Francis,Stephen D Kachman

doi:10.3390/microorganisms8020263

Abstract

Enterohemorrhagic Escherichia coli (EHEC), a pathogenic subset of Shiga toxin-producing E. coli (STEC), is an important cause of hemorrhagic colitis and hemolytic–uremic syndrome (HUS), and a rare cause of urinary tract infections (UTIs) with associated HUS. EHEC strains attach intimately to intestinal epithelium with formation of actin pedestals (attaching-effacing (A/E) lesions); however, the mechanism of EHEC attachment to the uroepithelium is unknown. We conducted a retrospective study on archived urinary bladder specimens from gnotobiotic piglets that naturally developed cystitis associated with EHEC O157:H7 infection following oral inoculation and fecal shedding. Paraffin-embedded bladder tissues from three piglets with cystitis and immunohistochemical evidence of EHEC O157:H7 adherence to the uroepithelium were processed for and examined by transmission electron microscopy. EHEC O157:H7 bacteria were found in one of three piglets, intimately attached to pedestals on the apical surfaces of the superficial urothelium (umbrella cells). Cystitis was significantly associated with the length of survival of the piglets post-inoculation (p = 0.0339; estimated odds ratio = 2.6652). This is the first report of E. coli causing A/E-like lesions in the uroepithelium, and also evidence of the utility of the gnotobiotic piglet as a model for studies of the pathogenesis of EHEC UTIs.

Highlights

Shiga toxin-producing Escherichia coli (STEC) is an important cause of foodborne illness in many countries of the world [1]
Non-O157 STEC were recognized as important causes of hemorrhagic colitis and hemolytic–uremic syndrome (HUS) [7]
STEC strains isolated from human patients with hemorrhagic colitis or HUS, and those isolated from any source that carry genes that encode for virulence factors that allow them to colonize the intestine, e.g., eae, are known as enterohemorrhagic E. coli (EHEC) [11]

Summary

Introduction

Shiga toxin-producing Escherichia coli (STEC) is an important cause of foodborne illness in many countries of the world [1]. STEC infections often cause hemorrhagic colitis and subsequent hemolytic–uremic syndrome (HUS) [2,3]. Non-O157 STEC were recognized as important causes of hemorrhagic colitis and HUS [7]. STEC strains isolated from human patients with hemorrhagic colitis or HUS, and those isolated from any source that carry genes that encode for virulence factors that allow them to colonize the intestine, e.g., eae (intimin), are known as enterohemorrhagic E. coli (EHEC) [11]. With regard to the urinary tract, the most common cause of uncomplicated infections is uropathogenic E. coli (UPEC), which accounts for approximately 90% of the cases [13,14,15]. We retrospectively conducted statistical analyses on clinical data of the piglets and found that the incidence of cystitis was significantly associated with the length of survival post-inoculation (PI)

Bacterial Strains and Gnotobiotic Piglet Studies

Transmission Electron Microscopy

Results and Discussion