Comparative genomics of Shiga toxin-producing Escherichia coli reveals host-specific adhesiome adaptations in humans and cattle

Authors: MARTINEZ, VICTOR - Universidad De Chile; CARTAJENA, JOSÉ - Universidad De Chile; MÉNDEZ, ESTEFANIA - Universidad De Chile; DÖRNER5, JESSICA - Universidad De Chile; MÉNDEZ, DIEGO - Universidad De Chile; ARRIAGADA, GABRIEL - O'Higgins University; TOLEDO, JORGE - Universidad De Chile; ARANCIBIA, RICHARD - O'Higgins University; PIZARRO, NICOLÁS - Instituto Nacional De Investigaciones Forestales Y Agropecuarias (INIFAP); CASTRO, DANIELA - Catholic University Of Maule; LUNA, DANIELA - Universidad De Chile; RAMOS, ROMINA - Universidad Andres Bello (UNAB); JORQUERA, JOAQUÍN - Universidad Andres Bello (UNAB); ESCOBAR, BEATRIZ - Universidad De Chile; Kudva, Indira; GALARCE, NICOLÁS - Universidad De Chile

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/19/2025
Publication Date: N/A
Citation: N/A

Interpretive Summary: Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens that are found in cattle but only cause serious infections in humans. STEC attachment to host intestinal cells is key to STEC survival in the host and subsequent spread. Most research has focused on STEC attachment to human intestinal cells rather than cattle. In this study, that information gap was addressed by analyzing the genomic DNA of 71 STEC isolated from feces of 948 Chilean cattle. The genomes of these STEC isolates were compared to global STEC genome sequences that are available online to spot any host-specific attachment gene distribution patterns. The comparative analysis identified STEC attachment genes that are common to cattle versus human STEC isolates. Additional variations in biological processes related to attachment that differed between hosts were determined. This research opens up new possibilities for methods to prevent the spread of STEC, especially from cattle to humans, with the identified host specific attachment-related genes being potential intervention targets.

Technical Abstract: Shiga toxin-producing Escherichia coli (STEC) is a zoonotic pathogen responsible for severe human infections, with cattle as its primary reservoir. Adhesion is a critical step in STEC colonization, facilitating persistence and transmission. While human-associated adhesion mechanisms have been extensively studied, those driving colonization in cattle remain less understood. In this study, we characterized the adhesiome of STEC strains isolated from Chilean cattle and compared them with a global collection to identify host-specific adhesion patterns and genetic adaptations. A total of 948 fecal samples from Chilean cattle were screened, yielding 71 confirmed STEC isolates, which were analyzed alongside 546 publicly available genomes to compare host-specific adhesion patterns. The adhesiome was examined based on gene presence/absence patterns, followed by a genome-wide association study (GWAS) and variant effect analysis to identify host-specific adhesion genes and their functional implications. Adhesin gene analysis revealed distinct adhesion strategies between hosts. Several genes, including ehaA, stgABC, yadLMN, and iha, were significantly associated with cattle, while eae, cah, ypjA, and paa were more frequent in human-associated STEC. Functional enrichment analysis revealed differences in biological processes, including protein folding and fimbrial usher porin activity in cattle, and response to methylglyoxal in humans GWAS identified yeeJ, espP, and fimC as strongly associated with cattle strains, whereas clpV, ybgQ, and sab were linked to human isolates. Variant analysis showed higher genetic diversity in human isolates, with yadK, espP, and ybgP exhibiting the highest variant densities. However, the functional effects of adhesin mutations were largely conserved across hosts, suggesting selective constraints on adhesion mechanisms. Our findings provide new insights into STEC host adaptation and highlight potential targets for pre-harvest intervention strategies to reduce zoonotic transmission. Future research should focus on functional validation of host-specific adhesin variants and their potential as preventive strategies.