Molecular and Phenotypic Characterization of Escherichia coli Associated with Granulomatous Colitis of Boxer Dogs.

Belgin Dogan,Cindy Guo,Kenneth W Simpson,Esra I Dogan,Sarah E Kalla,Chelston R Ang,Shiying Zhang

doi:10.3390/antibiotics9090540

Abstract

Invasive Escherichia coli is causally associated with granulomatous colitis (GC) of Boxer dogs and French Bulldogs. The virulence determinants of GC E. coli are unclear. E. coli isolated from 16 GC (36 strains) and 17 healthy control (HC: 33 strains) dogs were diverse in phylogeny, genotype, and serotype and lacked diarrheagenic genes. Genes encoding type II (gsp), IV (traC), and VI (hcp) secretion systems, long polar fimbriae (lpfA154/141), and iron acquisition (fyuA, chuA) were frequent in GC and HC. E. coli from 14/15 GC and 10/11 HC invaded Caco-2 better than non-pathogenic E. coli strain DH5α, with invasion correlated with motility and presence of chuA and colV. E. coli from all GC and 10/11 HC survived better than DH5α in J774 macrophages, with adherent-invasive E. coli (AIEC) in 60% GC and 73% HC. AIEC replicated in monocyte derived macrophages from a GC Boxer with CD48/SLAM risk haplotype but not the HC. Fluroquinolone resistant E. coli were less motile and invasive than fluoroquinolone sensitive (p < 0.05), and only 1/8 resistant strains met criteria for AIEC. In conclusion GC E. coli are diverse, resemble extraintestinal pathogenic E. coli (ExPEC), including AIEC, and can replicate in GC-susceptible macrophages. They are likely resident pathosymbionts that can opportunistically persist within macrophages of a GC-susceptible dog.

Highlights

Invasive Escherichia coli is causally associated with periodic acid-Schiff (PAS)-positive granulomatous colitis (GC) of Boxer dogs, French Bulldogs, and other breeds in the mastiff cluster [1,2,3].Eradication of invasive E. coli with macrophage penetrating antimicrobials, such as fluoroquinolones and chloramphenicol, can induce clinical cures and long-term remission [1,4]
E. coli from GC and healthy control (HC) dogs spanned the A, B1, B2, and D phylogenetic space (GC: 22% A, 36% B1, 17% B2, 25% D and HC: 6% A, 30% B1, 42% B2, 21% D)
Relatedness, and virulence of coli and their relationships to strains from healthyon dogs associated adherent-invasive E. coli (AIEC) to persist in monocyte-derived macrophages (MDMs) from GC and HC, the effect of fluoroquinolone resistance (HC)

Summary

Introduction

Invasive Escherichia coli is causally associated with periodic acid-Schiff (PAS)-positive granulomatous colitis (GC) of Boxer dogs, French Bulldogs, and other breeds in the mastiff cluster [1,2,3].Eradication of invasive E. coli with macrophage penetrating antimicrobials, such as fluoroquinolones and chloramphenicol, can induce clinical cures and long-term remission [1,4]. Invasive Escherichia coli is causally associated with periodic acid-Schiff (PAS)-positive granulomatous colitis (GC) of Boxer dogs, French Bulldogs, and other breeds in the mastiff cluster [1,2,3]. The presence and regional distribution of granulomatous inflammation in the colon and ileum of dogs with E. coli-associated. The presence of PAS-positive macrophages in canine E. coli-associated GC parallels intestinal inflammation in chronic granulomatous disease (CGD) and Whipple’s disease in people, which are associated with persistent intracellular bacterial infections [8,9,10,11,12]. The predilection of GC for Boxers and French Bulldogs

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