Role of the Nitric Oxide Reductase NorVW in the Survival and Virulence of Enterohaemorrhagic Escherichia coli during Infection.

Marion Gardette,Estelle Loukiadis,Julien Daniel,Grégory Jubelin

doi:10.3390/pathogens9090683

Abstract

Enterohaemorrhagic Escherichia coli (EHEC) are bacterial pathogens responsible for life-threatening diseases in humans, such as hemolytic and uremic syndrome. It has been previously demonstrated that the interplay between EHEC and nitric oxide (NO), a mediator of the host immune innate response, is critical for infection outcome, since NO affects both Shiga toxin (Stx) production and adhesion to enterocytes. In this study, we investigated the role of the NO reductase NorVW in the virulence and fitness of two EHEC strains in a murine model of infection. We determined that the deletion of norVW in the strain O91:H21 B2F1 has no impact on its virulence, whereas it reduces the ability of the strain O157:H7 620 to persist in the mouse gut and to produce Stx. We also revealed that the fitness defect of strain 620 ΔnorVW is strongly attenuated when mice are treated with an NO synthase inhibitor. Altogether, these results demonstrate that the NO reductase NorVW participates in EHEC resistance against NO produced by the host and promotes virulence through the modulation of Stx synthesis. The contribution of NorVW in the EHEC infectious process is, however, strain-dependent and suggests that the EHEC response to nitrosative stress is complex and multifactorial.

Highlights

Enterohaemorrhagic Escherichia coli (EHEC) are foodborne pathogens responsible for intestinal disorders in humans that can evolve into life-threatening diseases, such as hemorrhagic colitis and hemolytic-uremic syndrome (HUS) [1,2,3]
We determined the norV status in 34 EHEC strains belonging to different serotypes frequently involved in human infection (Table 1)
These data are consistent with previous results, indicating that the truncated form of the norV gene is strictly detected in the O157:H7 strains [19,26]

Summary

Introduction

Enterohaemorrhagic Escherichia coli (EHEC) are foodborne pathogens responsible for intestinal disorders in humans that can evolve into life-threatening diseases, such as hemorrhagic colitis and hemolytic-uremic syndrome (HUS) [1,2,3]. B subunits are required for binding at the surface of target cells [8]. Once produced in the gut, Stx crosses the intestinal epithelial barrier and gains access to the systemic circulation, where it targets the glycolipid globotriaosylceramide-3 (Gb3) receptors of endothelial cells [9]. The internalization of Stx alters the ribosomal function and induces the necrosis or apoptosis of vascular endothelial cells, leading to symptoms such as hemorrhagic colitis and HUS [10]. EHEC can produce two distinct forms of Pathogens 2020, 9, 683; doi:10.3390/pathogens9090683 www.mdpi.com/journal/pathogens

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