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GAS pathogenesis is complex, involving genetically distinct GAS strains and multiple infection sites. To overcome fastidious genetic manipulations and accelerate pathogenesis investigations in GAS, we developed a\n                    <jats:italic>mariner<\/jats:italic>\n                    -based system (\n                    <jats:italic>Krmit<\/jats:italic>\n                    ) for\n                    <jats:italic>en masse<\/jats:italic>\n                    monitoring of complex mutant pools by transposon sequencing (Tn-seq). Highly saturated transposant libraries (\n                    <jats:italic>Krmit<\/jats:italic>\n                    insertions in\n                    <jats:italic>ca<\/jats:italic>\n                    . every 25 nucleotides) were generated in two distinct GAS clinical isolates, a serotype M1T1 invasive strain 5448 and a nephritogenic serotype M49 strain NZ131 and analyzed using a Bayesian statistical model to predict GAS essential genes, identifying sets of 227 and 241 of those genes in 5448 and NZ131, respectively. A large proportion of GAS essential genes corresponded to key cellular processes and metabolic pathways and 177 were found conserved within the GAS core genome established from 20 available GAS genomes. Selected essential genes were validated using conditional-expression mutants. Finally, comparison to previous essentiality analyses in\n                    <jats:italic>S. sanguinis<\/jats:italic>\n                    and\n                    <jats:italic>S. pneumoniae<\/jats:italic>\n                    revealed significant overlaps, providing valuable insights for the development of new antimicrobials to treat infections by GAS and other pathogenic streptococci.\n                  <\/jats:p>","DOI":"10.1038\/srep09838","type":"journal-article","created":{"date-parts":[[2015,5,21]],"date-time":"2015-05-21T12:48:27Z","timestamp":1432212507000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":134,"title":["Essential Genes in the Core Genome of the Human Pathogen Streptococcus pyogenes"],"prefix":"10.1038","volume":"5","author":[{"given":"Yoann","family":"Le Breton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashton T.","family":"Belew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla M.","family":"Valdes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emrul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Curry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Tettelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Shirtliff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najib M.","family":"El-Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin S.","family":"McIver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,5,21]]},"reference":[{"key":"BFsrep09838_CR1","doi-asserted-by":"crossref","unstructured":"Carapetis, J. 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