{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:26:12Z","timestamp":1777922772782,"version":"3.51.4"},"reference-count":34,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>\n                    Penicillin-resistant\n                    <jats:italic toggle=\"yes\">Streptococcus pneumoniae<\/jats:italic>\n                    is a serious concern worldwide. In this study, we analyzed the cause of \u03b2-lactam resistance in pandemic multidrug-resistant clones. A total of 41 penicillin-nonsusceptible clinical isolates were collected from 1996 to 2012. Sero- and molecular typing confirmed that these isolates were clonal types of Taiwan\n                    <jats:sup>19F<\/jats:sup>\n                    -14, Taiwan\n                    <jats:sup>23F<\/jats:sup>\n                    -15, and Spain\n                    <jats:sup>23F<\/jats:sup>\n                    -1. Sero-switching was found in four isolates. All isolates were multidrug resistant. Sequencing analysis of the penicillin binding proteins (PBPs) was performed on PBP1a, 2b, and 2x, and a large number of mutations were identified in comparing to clinical penicillin-susceptible isolates and the recipient strain R6 used for homologous recombination. The T\n                    <jats:sub>451<\/jats:sub>\n                    A substitution was the key amino acid in PBP2b that contributed to penicillin resistance. T\n                    <jats:sub>338<\/jats:sub>\n                    A in PBP2x played a role in resistance and reached the highest level of resistance when combined with other mutations in PBP2x. High-level penicillin resistance could not be obtained without the combination of mutations in PBP1a with PBP2b and 2x. The amino acid substitutions in PBP1a, 2b, and 2x were the crucial factors for \u03b2-lactam resistance.\n                  <\/jats:p>","DOI":"10.1089\/mdr.2015.0261","type":"journal-article","created":{"date-parts":[[2016,4,4]],"date-time":"2016-04-04T17:49:12Z","timestamp":1459792152000},"page":"646-654","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Important Mutations Contributing to High-Level Penicillin Resistance in Taiwan\n                    <sup>19F<\/sup>\n                    -14, Taiwan\n                    <sup>23F<\/sup>\n                    -15, and Spain\n                    <sup>23F<\/sup>\n                    -1 of\n                    <i>Streptococcus pneumoniae<\/i>\n                    Isolated from Taiwan"],"prefix":"10.1177","volume":"22","author":[{"given":"Esther Yip-Mei","family":"Liu","sequence":"first","affiliation":[{"name":"National Yang-Ming University","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jen-Chang","family":"Chang","sequence":"additional","affiliation":[{"name":"National Health Research Institutes","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Chung","family":"Lin","sequence":"additional","affiliation":[{"name":"National Defense Medical Center","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng-Yee","family":"Chang","sequence":"additional","affiliation":[{"name":"National Defense Medical Center","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Phone","family":"Fung","sequence":"additional","affiliation":[{"name":"National Yang-Ming University","place":["Taiwan"]},{"name":"Taipei Veterans General Hospital and National Yang-Ming University","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,12]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/15.1.77"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","first-page":"395","DOI":"10.2217\/fmb.12.2","article-title":"Molecular mechanisms of beta-lactam resistance in Streptococcus pneumoniae","volume":"7","author":"Hakenbeck R.","year":"2012","unstructured":"Hakenbeck R., , Bruckner R., , Denapaite D., , and Maurer P. 2012. Molecular mechanisms of beta-lactam resistance in Streptococcus pneumoniae. Future Microbiol., 7:395\u2013410.","journal-title":"Future Microbiol."},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.3201\/eid0812.020178","article-title":"Antimicrobial resistance in Streptococcus pneumoniae, Taiwan","volume":"8","author":"Hsueh P.R.","year":"2002","unstructured":"Hsueh P.R., , and Luh K.T. 2002. Antimicrobial resistance in Streptococcus pneumoniae, Taiwan. Emerg. Infect. Dis., 8:1487\u20131491.","journal-title":"Emerg. Infect. Dis."},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0732-8893(98)00047-9","article-title":"Molecular epidemiology of penicillin-resistant Streptococcus pneumoniae isolated in central Taiwan","volume":"31","author":"Liu P.Y.","year":"1998","unstructured":"Liu P.Y., , Hu B.S., , Fung C.P., , Lau Y.J., , Shi Z.Y., , and Lin Y.H. 1998. Molecular epidemiology of penicillin-resistant Streptococcus pneumoniae isolated in central Taiwan. Diagn. Microbiol. Infect. Dis., 31:511\u2013515.","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"e_1_3_3_6_2","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.1128\/JCM.36.12.3514-3519.1998","article-title":"Identification of three major clones of multiply antibiotic-resistant Streptococcus pneumoniae in Taiwanese hospitals by multilocus sequence typing","volume":"36","author":"Shi Z.Y.","year":"1998","unstructured":"Shi Z.Y., , Enright M.C., , Wilkinson P., , Griffiths D., , and Spratt B.G. 1998. Identification of three major clones of multiply antibiotic-resistant Streptococcus pneumoniae in Taiwanese hospitals by multilocus sequence typing. J. Clin. Microbiol., 36:3514\u20133519.","journal-title":"J. Clin. 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