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Transformation frequency differs greatly among pneumococcal clinical isolates, but the molecular basis and biological importance of this interstrain variability remain unclear. In this study, we characterized the transformation frequency and other associated phenotypes of 208\n            <jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>\n            clinical isolates representing at least 30 serotypes. While the vast majority of these isolates (94.7%) were transformable, the transformation frequency differed by up to 5 orders of magnitude between the least and most transformable isolates. The strain-to-strain differences in transformation frequency were observed among many isolates producing the same capsule types, indicating no general association between transformation frequency and serotype. However, a statistically significant association was observed between the levels of transformation and colonization fitness\/virulence in the hypertransformable isolates. Although nontransformable mutants of all the selected hypertransformable isolates were significantly attenuated in colonization fitness and virulence in mouse infection models, such mutants of the strains with relatively low transformability had no or marginal fitness phenotypes under the same experimental settings. This finding strongly suggests that the pneumococci with high transformation capability are \u201caddicted\u201d to a \u201chypertransformable\u201d state for optimal fitness in the human host. This work has thus provided an intriguing hint for further investigation into how the competence system impacts the fitness, virulence, and other transformation-associated traits of this important human pathogen.\n          <\/jats:p>","DOI":"10.1128\/iai.00097-16","type":"journal-article","created":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T03:23:49Z","timestamp":1460431429000},"page":"1887-1901","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Addiction of Hypertransformable Pneumococcal Isolates to Natural Transformation for\n            <i>In Vivo<\/i>\n            Fitness and Virulence"],"prefix":"10.1128","volume":"84","author":[{"given":"Guiling","family":"Li","sequence":"first","affiliation":[{"name":"Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuowen","family":"Liang","sequence":"additional","affiliation":[{"name":"Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiatai","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing Children's Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhujun","family":"Shao","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machao","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyun","family":"Ma","sequence":"additional","affiliation":[{"name":"Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Qu","sequence":"additional","affiliation":[{"name":"The Center of Clinical Diagnosis, The 302 Hospital of PLA, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald A.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Ren","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China"},{"name":"Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(04)00938-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2014.01.002"},{"key":"e_1_3_3_4_2","first-page":"275","volume-title":"Gram-positive pathogens","author":"Yother J","year":"2006","unstructured":"Yother J. 2006. 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