Differential Outcome between BALB/c and C57BL/6 Mice after Escherichia coli O157:H7 Infection Is Associated with a Dissimilar Tolerance Mechanism.

Andreas J. Bäumler,Alan M. Bernal,Martin Rumbo,María Victoria Ramos,Andrea Cecilia Bruballa,Gonzalo Ezequiel Pineda,Gabriela A. Fiorentino,Elsa Zotta,Mónica Vermeulen,Marina Sandra Palermo,Romina Jimena Fernández-Brando

doi:10.1128/iai.00031-21

Abstract

Enterohemorrhagic Escherichia coli (EHEC) infections can result in a wide range of clinical presentations despite that EHEC strains belong to the O157:H7 serotype, one of the most pathogenic forms. Although pathogen virulence influences disease outcome, we emphasize the concept of host-pathogen interactions, which involve resistance or tolerance mechanisms in the host that determine total host fitness and bacterial virulence. Taking advantage of the genetic differences between mouse strains, we analyzed the clinical progression in C57BL/6 and BALB/c weaned mice infected with an E. coli O157:H7 strain. We carefully analyzed colonization with several bacterial doses, clinical parameters, intestinal histology, and the integrity of the intestinal barrier, as well as local and systemic levels of antibodies to pathogenic factors. We demonstrated that although both strains had comparable susceptibility to Shiga toxin (Stx) and the intestinal bacterial burden was similar, C57BL/6 showed increased intestinal damage, alteration of the integrity of the intestinal barrier, and impaired renal function that resulted in increased mortality. The increased survival rate in the BALB/c strain was associated with an early specific antibody response as part of a tolerance mechanism.

Highlights

Enterohemorrhagic Escherichia coli (EHEC) infections can result in a wide range of clinical presentations despite that EHEC strains belong to the O157:H7 serotype, one of the most pathogenic forms
As intestinal colonization is the first step in the pathogenic cascade that leads to systemic illness, we analyzed the level of O157:H7 intestinal colonization versus the infective dose for both mouse strains
O157:H7 CFU recovered from cecum, small intestine, and large intestine of BALB/c mice at day 3 p.i. showed a positive correlation with the inoculum in the three intestinal segments (r = 0.65, P, 0.05; r = 0.90, P, 0.001; and r = 0.84, P, 0.01, respectively)

Summary

Introduction

Enterohemorrhagic Escherichia coli (EHEC) infections can result in a wide range of clinical presentations despite that EHEC strains belong to the O157:H7 serotype, one of the most pathogenic forms. Taking advantage of the genetic differences between mouse strains, we analyzed the clinical progression in C57BL/6 and BALB/c weaned mice infected with an E. coli O157:H7 strain. In Argentina, as well as in other countries, E. coli O157:H7 is the most common EHEC serotype associated with the systemic complication hemolytic uremic syndrome (HUS) [2] It is not clear why EHEC infections, even those caused by the O157:H7 strain, can result in a wide range of clinical presentations, from healthy carriers and watery diarrhea to HUS [1,2,3]. Taking advantage of the genetic differences between mouse strains, we analyzed the clinical progression in C57BL/6 (C57) and BALB/c mice infected with an O157: H7 strain belonging to clade 8. We preferred this model over the antibiotic-treated or gnotobiotic mouse models, in which sensitivity of adult mice to EHEC infection is reached by the absence of competence with resident microbiota, as this is an important component of defense mechanisms against pathogens

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Conclusion