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Campylobacter is the leading cause of bacterial gastroenteritis worldwide and an emerging and neglected pathogen in South America. This zoonotic pathogen colonizes the gastrointestinal tract of a wide range of mammals and birds, with poultry as the most important reservoir for human infections. Apart from its high morbidity rates, the emergence of resistant strains is of global concern. The aims of this work were to determine genetic diversity, presence of antimicrobial resistance determinants and virulence potential of Campylobacter spp. isolated from patients with acute gastrointestinal disease at 'Clinica Alemana', Santiago de Chile. The study considered the isolation of Campylobacter spp., from stool samples during a 20-month period (January 2020 to September 2021). We sequenced (NextSeq, Illumina) and performed an in-depth analysis of the genome sequences of 88 Campylobacter jejuni and 2 Campylobacter coli strains isolated from clinical samples in Chile. We identified a high genetic diversity among C. jejuni strains and the emergence of prevalent clonal complexes, which were not identified in our previous reports. While ~40% of strains harbored a mutation in the gyrA gene associated with fluoroquinolone resistance, no macrolide-resistance determinants were detected. Interestingly, gene clusters encoding virulence factors such as the T6SS or genes associated with long-term sequelae such as Guillain-Barré syndrome showed lineage-relatedness. In addition, our analysis revealed a high degree of variability regarding the presence of fT3SS and T6SS effector proteins in comparison to type strains 81-176, F38011, and NCTC 11168 and 488. Our study provides important insights into the molecular epidemiology of this emerging foodborne pathogen. In addition, the differences observed regarding the repertoire of fT3SS and T6SS effector proteins could have an impact on the pathogenic potential and transmissibility of these Latin American isolates, posing another challenge in characterizing the infection dynamics of this emergent and neglected bacterial pathogen. [ABSTRACT FROM AUTHOR]