Chaperone-Usher Pili Loci of Colonization Factor-Negative Human Enterotoxigenic Escherichia coli.

Felipe Del Canto,Mihai Pop,Daniela Hernández,David A Rasko,Myron M Levine,Alexia Torres,Raul Valdés,Roberto Vidal,Daniela Gutiérrez,Miguel O'Ryan,Aquiles Mansilla,Rodrigo Martínez,Christopher M Hill,O Colin Stine,Leandro Cádiz,Benjamin Caro,Mirka Pardo

doi:10.3389/fcimb.2016.00200

Abstract

Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhea worldwide. Among the 25 different ETEC adhesins, 22 are known as “colonization factors” (CFs), of which 17 are assembled by the chaperone-usher (CU) mechanism. Currently, there is no preventive therapy against ETEC, and CFs have been proposed as components for vaccine development. However, studies of diarrhea-causing ETEC strains worldwide indicate that between 15 and 50% of these are negative for known CFs, hindering the selection of the most widespread structures and suggesting that unknown adhesins remain to be identified. Here, we report the result of a comprehensive analysis of 35 draft genomes of ETEC strains which do not carry known adhesin genes; our goal was to find new CU pili loci. The phylogenetic profiles and serogroups of these strains were highly diverse, a majority of which produced only the heat-labile toxin. We identified 10 pili loci belonging to CU families β (1 locus), γ2 (7 loci), κ (1 locus), and π (1 locus), all of which contained the required number of open reading frames (ORFs) to encode functional structures. Three loci were variants of previously-known clusters, three had been only-partially described, and four are novel loci. Intra-loci genetic variability identified would allow the synthesis of up to 14 different structures. Clusters of putative γ2-CU pili were most common (23 strains), followed by putative β-CU pili (12 strains), which have not yet been fully characterized. Overall, our findings significantly increase the number of ETEC adhesion genes associated with human infections.

Highlights

Enterotoxigenic Escherichia coli (ETEC), which includes a wide diversity of strains, are one of six categories of diarrheagenic E. coli (Croxen et al, 2013)
Thirty five ETEC strains were included in the study, each of which were considered negative for known adhesins (ANETEC), because no product was obtained in PCR analyses aimed at detecting loci encoding CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, CS7, CS8, CS12, CS13, CS14, CS15, CS17, CS18, CS19, CS20, CS21, CS22, CS23, Tia, TibA, or EtpA
Thirty-five AN-ETEC strains genomes were sequenced in order to identify putative adhesin loci

Summary

Introduction

Enterotoxigenic Escherichia coli (ETEC), which includes a wide diversity of strains, are one of six categories of diarrheagenic E. coli (Croxen et al, 2013). These ETEC are a common cause of watery diarrhea worldwide, primarily affecting children living in resource-poor settings of developing countries and travelers who visit these endemic regions (Qadri et al, 2005). CF-Negative ETEC Chaperone-Usher Pili Loci reservoir for ETEC; transmission is associated with consumption of food or water contaminated with human feces (Qadri et al, 2005). An essential part of infection is attachment to intestinal cells, which ETEC accomplish using a diverse array of adhesins; among these, colonization factors (CFs) have been the most studied to date (Croxen et al, 2013)

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