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The age dependency of infection can be reproduced in neonatal rats. Colonization of the small intestine following oral administration of K1 bacteria leads rapidly to invasion of the blood circulation; bacteria that avoid capture by the mesenteric lymphatic system and evade antibacterial mechanisms in the blood may disseminate to cause organ-specific infections such as meningitis. Some\n            <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n            K1 surface constituents, in particular the polysialic acid capsule, are known to contribute to invasive potential, but a comprehensive picture of the factors that determine the fully virulent phenotype has not emerged so far. We constructed a library and constituent sublibraries of \u223c775,000 Tn\n            <jats:italic>5<\/jats:italic>\n            transposon mutants of\n            <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n            K1 strain A192PP and employed transposon-directed insertion site sequencing (TraDIS) to identify genes required for fitness for infection of 2-day-old rats. Transposon insertions were lacking in 357 genes following recovery on selective agar; these genes were considered essential for growth in nutrient-replete medium. Colonization of the midsection of the small intestine was facilitated by 167\n            <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n            K1 gene products. Restricted bacterial translocation across epithelial barriers precluded TraDIS analysis of gut-to-blood and blood-to-brain transits; 97 genes were required for survival in human serum. This study revealed that a large number of bacterial genes, many of which were not previously associated with systemic\n            <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n            K1 infection, are required to realize full invasive potential.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            K1 strains cause life-threatening infections in newborn infants. They are acquired from the mother at birth and colonize the small intestine, from where they invade the blood and central nervous system. It is difficult to obtain information from acutely ill patients that sheds light on physiological and bacterial factors determining invasive disease. Key aspects of naturally occurring age-dependent human infection can be reproduced in neonatal rats. Here, we employ transposon-directed insertion site sequencing to identify genes essential for the\n            <jats:italic>in vitro<\/jats:italic>\n            growth of\n            <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n            K1 and genes that contribute to the colonization of susceptible rats. The presence of bottlenecks to invasion of the blood and cerebrospinal compartments precluded insertion site sequencing analysis, but we identified genes for survival in serum.\n          <\/jats:p>","DOI":"10.1128\/jb.00698-17","type":"journal-article","created":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T08:34:26Z","timestamp":1516005266000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":51,"title":["Genome-Wide Identification by Transposon Insertion Sequencing of Escherichia coli K1 Genes Essential for\n            <i>In Vitro<\/i>\n            Growth, Gastrointestinal Colonizing Capacity, and Survival in Serum"],"prefix":"10.1128","volume":"200","author":[{"given":"Alex J.","family":"McCarthy","sequence":"first","affiliation":[{"name":"School of Pharmacy, University College London, London, United 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