{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:23:30Z","timestamp":1784053410529,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T00:00:00Z","timestamp":1549238400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbiology and Immunology"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>In this study, the selective potential of group B <jats:italic>Streptococcus<\/jats:italic> isolates with reduced penicillin susceptibility (PRGBS) in a neonate\u2010hypervirulent sequence type (ST)17 lineage was investigated by <jats:italic>in vitro<\/jats:italic> exposure to \u03b2\u2010lactams. After 19 passages of stepwise penicillin exposure, PRGBS with a high penicillin minimum inhibitory concentration MIC (0.5\u2009mg\/L), greatly augmented ceftibuten MIC (&gt;512\u2009mg\/L), and acquisition of G406D predicted to provide destabilizing effect (\u0394\u0394G 0.099\u2009kcal\/mol) on PBP2X structure were identified. In early passages of stepwise cefotaxime exposure, PRGBS possessing G398E predicted to stabilize PBP2X (\u0394\u0394G \u22120.038\u2009kcal\/mol) emerged with high MICs for cefotaxime (0.5\u2009mg\/L), ceftibuten (&gt;512\u2009mg\/L) and penicillin (0.25\u2009mg\/L). Additionally, G398E\u2009+\u2009G329V\u2009+\u2009H438Y predicted to provide more stabilizing effect (\u0394\u0394G \u22120.415\u2009kcal\/mol) were detected in mutants with higher MICs to cefotaxime (1\u2009mg\/L) and penicillin (0.5\u2009mg\/L). PRGBS mutants selected by penicillin and cefotaxime had a marked growth disadvantage compared with the parent strain. After two passages of stepwise ceftibuten exposure, the mutants exhibited increased MICs toward ceftibuten and acquisition of T555S predicted to provide stabilizing effect (\u0394\u0394G \u22120.111\u2009kcal\/mol) in PBP 2X. In subsequent passages, gradual increases in ceftibuten MICs from 128\u2009mg\/L to 512\u2009mg\/L were found among selected mutants with accompanying stabilizing T555S+A354V (\u0394\u0394G \u22120.257\u2009kcal\/mol) followed by stabilizing T555S\u2009+\u2009A354V\u2009+\u2009A536V (\u0394\u0394G \u22120.322\u2009kcal\/mol), resulting in selection of a penicillin\u2010susceptible group B <jats:italic>Streptococcus<\/jats:italic> lineage with reduced ceftibuten susceptibility (CTB<jats:sup>r<\/jats:sup>PSGBS). Notably, growth ability of CTB<jats:sup>r<\/jats:sup>PSGBS mutants was comparable to that of the parent strain. These findings may predict future failure of treatment for neonatal invasive infections caused by the neonate\u2010hypervirulent PRGBS ST17 lineage.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1348-0421.12667","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T11:39:58Z","timestamp":1547206798000},"page":"65-76","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Potential effect of selective pressure with different \u03b2\u2010lactam molecules on the emergence of reduced susceptibility to \u03b2\u2010lactams in group B <i>Streptococci<\/i>"],"prefix":"10.1111","volume":"63","author":[{"given":"Shota","family":"Koide","sequence":"first","affiliation":[{"name":"Department of Health and Medical Sciences Shinshu University Graduate School of Medicine 3\u20101\u20101 Asahi Matsumoto Nagano 390\u20108621 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Health and Medical Sciences Shinshu University Graduate School of Medicine 3\u20101\u20101 Asahi Matsumoto Nagano 390\u20108621 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Health and Medical Sciences Shinshu University Graduate School of Medicine 3\u20101\u20101 Asahi Matsumoto Nagano 390\u20108621 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayato","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Health and Medical Sciences Shinshu University Graduate School of Medicine 3\u20101\u20101 Asahi Matsumoto Nagano 390\u20108621 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouji","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Bacteriology Nagoya University Graduate School of Medicine 65 Tsurumai\u2010cho, Showa\u2010ku Nagoya Aichi 466\u20108550 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Nagano","sequence":"additional","affiliation":[{"name":"Department of Bacteriology Nagoya University Graduate School of Medicine 65 Tsurumai\u2010cho, Showa\u2010ku Nagoya Aichi 466\u20108550 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshichika","family":"Arakawa","sequence":"additional","affiliation":[{"name":"Department of Bacteriology Nagoya University Graduate School of Medicine 65 Tsurumai\u2010cho, Showa\u2010ku Nagoya Aichi 466\u20108550 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Nagano","sequence":"additional","affiliation":[{"name":"Department of Health and Medical Sciences Shinshu University Graduate School of Medicine 3\u20101\u20101 Asahi Matsumoto Nagano 390\u20108621 Japan"},{"name":"Department of Medical Sciences Shinshu University Graduate School of Medicine Science and Technology 3\u20101\u20101 Asahi Matsumoto Nagano 390\u20108621 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.6.2530-2536.2003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092594"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00185-08"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00596-08"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp374"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr546"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks423"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00461-08"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp458"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01243-10"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02063-08"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01291-14"},{"key":"e_1_2_8_14_1","volume-title":"Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard","year":"2015"},{"key":"e_1_2_8_15_1","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing; Twenty\u2010Seven Informational Supplement","year":"2017"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh082"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.1.121"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku340"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv769"},{"key":"e_1_2_8_20_1","unstructured":"Swiss Institute of Bioinformatics Molecular Modelling Group. 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