title: Addiction of Hypertransformable Pneumococcal Isolates to Natural Transformation for In Vivo Fitness and Virulence.
abstract: Natural genetic transformation of Streptococcus pneumoniae, an important human pathogen, mediates horizontal gene transfer for the development of drug resistance, modulation of carriage and virulence traits, and evasion of host immunity. 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 S. pneumoniae 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 "addicted" to a "hypertransformable" 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.
authors.affiliation: Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Guiling
authors.initials: G
authors.lastname: Li
authors.affiliation: Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhuowen
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Xiatai
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Shao
authors.affiliation: 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.
authors.forename: Machao
authors.initials: M
authors.lastname: Li
authors.affiliation: Xijing Orthopaedics Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yueyun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: The Center of Clinical Diagnosis, The 302 Hospital of PLA, Beijing, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Qu
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Morrison
authors.affiliation: Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China zhanglab@tsinghua.edu.cn.|Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, China.
authors.forename: Jing-Ren
authors.initials: JR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000276:immunology*; D056084:Genetic Fitness; D018740:Genetic Heterogeneity; D006801:Humans; D057131:Immune Evasion / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009305:Nasopharynx / Q000276:immunology / Q000382:microbiology; D010641:Phenotype; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D014169:Transformation, Bacterial / Q000276:immunology*; D014774:Virulence