Comparative Genomics of Shiga Toxin-Producing Escherichia coli Reveals Host-Specific Adhesiome Adaptations in Humans and Cattle

Victor A Martinez¹José T Cartajena^2,3Estefanía Méndez⁴Jessica Dörner¹Diego Méndez^1,2Gabriel Arriagada⁵Jorge Toledo⁶Richard Arancibia⁷Nicolás Pizarro⁸Daniela Castro^10,9Daniela Luna¹Romina Ramos Ríos¹¹Joaquín Jorquera¹¹Beatriz Escobar²Indira T Kudva¹²Nicolás Galarce^2*

• ¹Departamento de Ciencia Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santiago, Chile
• ²Departamento de Medicina Preventiva Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santiago, Chile
• ³Programa de Magíster en Ciencias Animales y Veterinarias, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santiago, Chile
• ⁴PhD in Conservation Medicine, Life Sciences Faculty, Universidad Andres Bello, Santiago, Chile
• ⁵Instituto de Ciencias Agroalimentarias, Animales y Ambientales, Universidad de O’Higgins, San Fernando, Chile
• ⁶Red de Equipamiento Científico Avanzado, Facultad de Medicina, Universidad de Chile, Santiago, Chile
• ⁷Departamento de Ciencias Clínicas, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santiago, Chile
• ⁸Instituto de Investigaciones Agropecuarias, Osorno, Chile
• ⁹Escuela de Medicina Veterinaria, Facultad de Ciencias Agrarias y Forestales, Universidad Católica del Maule, Curicó, Chile
• ¹⁰Escuela de Medicina Veterinaria, Facultad de Recursos Naturales y Medicina Veterinaria, Universidad Santo Tomás, Santiago, Chile
• ¹¹Escuela de Medicina Veterinaria, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile
• ¹²Food Safety and Enteric Pathogens Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, United States

Shiga toxin-producing Escherichia coli (STEC) is a zoonotic pathogen responsible for severe human infections, with cattle recognized as the principal animal reservoir for human infection. 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 to reduce zoonotic transmission and improve pre-harvest food safety strategies. Future research should focus on functional validation of host-specific adhesin variants and their potential as preventive strategies.