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Strains from two internationally circulating sequence types, ST-7363 and ST-1901, have acquired resistance to third-generation cephalosporins, mainly due to mosaic\n                      <jats:italic>penA<\/jats:italic>\n                      alleles. These two STs were first detected in Japan; however, the timeline, mechanism, and process of emergence and spread of these mosaic\n                      <jats:italic>penA<\/jats:italic>\n                      alleles to other countries remain unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We studied the evolution of\n                      <jats:italic>penA<\/jats:italic>\n                      alleles by obtaining the complete genomes from three Japanese ST-1901 clinical isolates harboring mosaic\n                      <jats:italic>penA<\/jats:italic>\n                      allele 34 (\n                      <jats:italic>penA-<\/jats:italic>\n                      34) dating from 2005 and generating a phylogenetic representation of 1075 strains sampled from 35 countries. We also sequenced the genomes of 103 Japanese ST-7363\u2009\n                      <jats:italic>N. gonorrhoeae<\/jats:italic>\n                      isolates from 1996 to 2005 and reconstructed a phylogeny including 88 previously sequenced genomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Based on an estimate of the time-of-emergence of ST-1901 (harboring mosaic\n                      <jats:italic>penA-34<\/jats:italic>\n                      ) and ST-7363 (harboring mosaic\n                      <jats:italic>penA<\/jats:italic>\n                      -10), and &gt;\u2009300 additional genome sequences of Japanese strains representing multiple STs isolated in 1996\u20132015, we suggest that\n                      <jats:italic>penA<\/jats:italic>\n                      -34 in ST-1901 was generated from\n                      <jats:italic>penA<\/jats:italic>\n                      -10 via recombination with another\n                      <jats:italic>Neisseria<\/jats:italic>\n                      species, followed by recombination with a gonococcal strain harboring wildtype\n                      <jats:italic>penA<\/jats:italic>\n                      -1. Following the acquisition of\n                      <jats:italic>penA<\/jats:italic>\n                      -10 in ST-7363, a dominant sub-lineage rapidly acquired fluoroquinolone resistance mutations at GyrA 95 and ParC 87-88, by independent mutations rather than horizontal gene transfer. Data in the literature suggest that the emergence of these resistance determinants may reflect selection from the standard treatment regimens in Japan at that time.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings highlight how antibiotic use and recombination across and within\n                      <jats:italic>Neisseria<\/jats:italic>\n                      species intersect in driving the emergence and spread of drug-resistant gonorrhea.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13073-021-00860-8","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T06:03:16Z","timestamp":1617084196000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Emergence and evolution of antimicrobial resistance genes and mutations in Neisseria gonorrhoeae"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4289-1115","authenticated-orcid":false,"given":"Koji","family":"Yahara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C.","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatum D.","family":"Mortimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Shimuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-ichi","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki","family":"Hirabayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Jinnai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Ohya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiro","family":"Kuroki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Deguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vegard","family":"Eldholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile B.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin C. 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