Identification of a genomic cluster related to hypersecretion of intestinal mucus and mucinolytic activity of atypical enteropathogenic Escherichia coli (aEPEC)

Author(s)

Trovao, Liana de Oliveira ; Vieira, Monica Aparecida Midolli ; Santos, Ana Carolina de Mello ; Puno-Sarmiento, Juan Josue ; Nunes, Pedro Henrique Soares ; Santos, Fernanda Fernandes ; Rocha, Victoria Galdino Pavlenco ; Knobl, Terezinha ; Navarro-Garcia, Fernando ; Gomes, Tania Aparecida Tardelli

• Document type: Journal article
• Source: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 14, p. 17-pg., 2024-12-04.

Abstract

Enteropathogenic Escherichia coli (EPEC) strains are subdivided into typical (tEPEC) and atypical (aEPEC) according to the presence or absence of a virulence-associated plasmid called pEAF. Our research group has previously demonstrated that two aEPEC strains, 0421-1 and 3991-1, induce an increase in mucus production in a rabbit ileal loop model in vivo. This phenomenon was not observed with a tEPEC prototype strain. Few studies on aEPEC strains evaluating their capacity to induce intestinal mucus hypersecretion were done. This study aimed to investigate aEPEC strains regarding their genotypic and phenotypic characteristics, their ability to alter mucus production in an in vivo intestinal infection model, and their potential mucinolytic activity. To investigate the relationship between strains 0421-1 and 3991-1 and 11 other aEPEC strains, their serotypes, sequence types (ST), and virulence factors (VF), several sequencing and genomic analyses were carried out. The study also involved researching the reproduction of mucus hypersecretion in rabbits in vivo. We found that the two mucus-inducing strains and two other strains (1582-4 and 2531-13) shared the same phylogroup (A), ST (378), serotype (O101/O162:H33), and intimin subtype (iota 2), were phylogenetically related, and induced mucus hypersecretion in vivo. A wide diversity of VFs was found among the strains, confirming their genomic heterogeneity. However, among the genes studied, no unique virulence factor or gene set was identified exclusively in the mucus-inducing strains, suggesting the multifactorial nature of this phenomenon. The two strains (1582-4 and 2531-13) closely related to the two aEPEC strains that induced mucus production in vivo also induced the phenomenon. The investigation of the mucinolytic activity revealed that all aEPEC strains used mucins as their carbon sources. Ten of the 13 aEPEC strains could cross a mucin layer, and only four adhered better to agar containing mucin than to agar without mucin. The present study paves the way for subsequent investigations into the molecular mechanisms regarding cellular interactions and responses, as well as the correlation between virulence factors and the induction of mucus production/expression during aEPEC infections. (AU)

• FAPESP's process: 23/03097-7 - Standardization and validation of ex vivo rabbit intestinal loop and in vitro mucinolytic activity assays for investigation of mucus induction and mucinase production during infection with pathogenic Escherichia coli strains
• Grantee: Liana de Oliveira Trovão
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 22/12006-2 - Role of cytokines in modulating the induction of mucus production by atypical enteropathogenic Escherichia coli (aEPEC) strains in intestinal cells in vitro
• Grantee: Juan Josue Puño Sarmiento
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/14821-7 - Exploring novel virulence strategies in Escherichia coli
• Grantee: Tânia Aparecida Tardelli Gomes do Amaral
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 23/05910-7 - Genetic and bioinformatic approaches for comparative and functional analysis of the genome and plasmid of typical EAEC strains isolated from urinary tract infections.
• Grantee: Ana Carolina de Mello Santos Gheller
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training