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ExPEC includes the pathotypes avian pathogenic\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      (APEC), neonatal meningitis\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      (NMEC), sepsis-associated\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      (SEPEC), and uropathogenic\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      (UPEC). These pathotypes share multiple virulence factors, including the Type VI Secretion System (T6SS), a nanomachinery that has been described as important for\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      pathogenesis. In this study, we applied genome-wide association analysis to evaluate the prevalence and evolution of T6SS across 399 ExPEC genomes, including new NMEC (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 78) and APEC (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 68) sequences (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 146). Our findings suggest that among ExPEC, T6SS is more prevalent in NMEC and is more conserved between NMEC and APEC in terms of loci organization and gene content, whereas greater structural variation was observed in SEPEC and UPEC. Additionally, our findings indicate an inverse relationship between T6SS presence and antimicrobial resistance, suggesting that harboring both may incur a fitness cost. Our study provides new insights into the ecological and evolutionary pressures shaping the distribution of T6SS among ExPEC lineages and supports its relevance for further\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      investigation regarding its expression and function in\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Extraintestinal pathogenic\n                        <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                        (ExPEC) is responsible for severe infections in humans and animals. However, the distribution of the Type VI Secretion System (T6SS) among these pathotypes remains unclear. The T6SS has been implicated in\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        pathogenicity, but its prevalence and structural diversity across ExPEC are still poorly understood due to the lack of genomes available from some pathotypes, especially neonatal meningitis\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        (NMEC) strains. This study introduces new NMEC and avian pathogenic\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        (APEC) genomes among a total of 399 ExPEC genomes analyzed, including sepsis-associated\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        (SEPEC) and uropathogenic\n                        <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                        (UPEC). Our findings indicate the T6SS as a conserved and predominant virulence factor in NMEC compared with other pathotypes. Moreover, an inverse association between T6SS presence and antimicrobial resistance suggests a potential fitness trade-off that may influence ExPEC evolution. These findings advance our understanding of T6SS in ExPEC and identify this secretion system as a relevant target for future functional and mechanistic studies.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.04033-25","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T13:00:19Z","timestamp":1782392419000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Genomic characterization of the type VI secretion system in extraintestinal pathogenic\n                    <i>Escherichia coli<\/i>"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9217-6913","authenticated-orcid":true,"given":"Julia","family":"Ienes-Lima","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bjhwk41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Population Health, College of Veterinary Medicine, University of Georgia","place":["Athens, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5353-2081","authenticated-orcid":true,"given":"Sonsiray","family":"\u00c1lvarez-Narv\u00e1ez","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bjhwk41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia","place":["Athens, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolle Lima","family":"Barbieri","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bjhwk41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Population Health, College of Veterinary Medicine, University of Georgia","place":["Athens, 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