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Pan-genome analysis was used to identify flexible genomic islands associated with in-hospital attributable mortality. Genomic islands of interest were investigated experimentally.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 193 E. coli genomes. Two genomic islands were co-present within 41 (21%) genomes and associated with increased attributable mortality in an adjusted analysis (Odds ratio 3.0; 95% confidence interval 1.1-7.9; p=0.03). The two genomic islands together contain genes homologous to a type III secretion system (T3SS): 1) E. coli type III secretion system 2 (ETT2), encoding genes homologous to a T3SS basal body and needle complex, and 2) an ETT2 accessory region (ETT2-AR) encoding genes homologous to a T3SS needle tip, translocases, and adhesin. ETT2\/ETT2-AR increased resistance to complement-mediated growth restriction by inhibiting classical complement pathway activation and impacted E. coli-host cell interactions by increasing adhesion to and death of mammalian cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Genomic islands ETT2 and ETT2-AR are homologous to a T3SS, co-localize within specific E. coli lineages, associate with increased mortality, and increase bacterial virulence through resistance to complement and enhanced host cell adhesion and death.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf265","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T21:58:46Z","timestamp":1747951126000},"page":"1097-1107","source":"Crossref","is-referenced-by-count":1,"title":["<i>Escherichia coli<\/i>\n                    Type III Secretion System 2 Is Associated With Patient Mortality in Bloodstream Infections"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3250-0697","authenticated-orcid":false,"given":"Joshua T","family":"Thaden","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip","family":"Cox","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paa Kwesi","family":"Ankrah","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Khandelwal","sequence":"additional","affiliation":[{"name":"Division of Hematology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9037-8418","authenticated-orcid":false,"given":"Jeffrey S","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, School of Medicine, Duke University , Durham, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orianna","family":"Poteete","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2176-6462","authenticated-orcid":false,"given":"Felicia","family":"Ruffin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0496-5064","authenticated-orcid":false,"given":"Gowthami","family":"Arepally","sequence":"additional","affiliation":[{"name":"Division of Hematology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Granger","family":"Sutton","sequence":"additional","affiliation":[{"name":"J. 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