Markus HiltyDaniel WüthrichSusannah J. SalterHansjürg EngelSamuel CampbellRaquel Sá-LeãoHermínia De LencastrePeter HermansEwa SadowyPaul TurnerClaire ChewapreechaMathew DiggleGerd PluschkeLesley McGeeÖzgen Köseoʇlu EserDonald E. LowHeidi Smith-VaughanAndrea EndimianiMarianne Kü FferMélanie DupasquierEmmanuel BeaudoingJohann WeberRémy BruggmannWilliam P. HanageJulian ParkhillLucy J. HathawayKathrin Mü HlemannStephen D. BentleyUniversity of BernUniversitatsSpital BernSwiss Institute of BioinformaticsWellcome Trust Sanger InstituteInstituto de Tecnologia Quimica e Biologica - Univesidade Nova de LisboaRockefeller UniversityRadboud University NijmegenNational Medicines Institute, WarsawMahidol UniversityNuffield Department of Clinical MedicineQueen's Medical CentreUniversitat BaselNational Center for Immunization and Respiratory DiseasesHacettepe UniversitesiMount Sinai Hospital of University of TorontoMenzies School of Health ResearchUniversitat Lausanne SchweizHarvard School of Public HealthUniversity of Cambridge2018-11-092018-11-092014-01-01Genome Biology and Evolution. Vol.6, No.12 (2014), 3281-3294175966532-s2.0-84933510790https://repository.li.mahidol.ac.th/handle/20.500.14594/33175© The Author(s) 2014. The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated S. pneumoniae (non-Ec-Sp) have also been isolated globally, mainly in carriage studies. It is unknown if non-Ec-Sp evolve sporadically, if they have high antibiotic nonsusceptiblity rates and a unique, specific gene content. Here, whole-genome sequencing of 131 non-Ec-Sp isolates sourced from 17 different locations around the world was performed. Results revealed a deep-branching classic lineage that is distinct from multiple sporadic lineages. The sporadic lineages clustered with a previously sequenced, global collection of encapsulated S. pneumoniae (Ec-Sp) isolates while the classic lineage is comprised mainly of the frequently identified multilocus sequences types (STs) ST344 (n = 39) and ST448 (n = 40). All ST344 and nine ST448 isolates had high nonsusceptiblity rates to β-lactams and other antimicrobials. Analysis of the accessory genome reveals that the classic non-Ec-Sp contained an increased number of mobile elements, than Ec-Sp and sporadic non-Ec-Sp. Performing adherence assays to human epithelial cells for selected classic and sporadic non-Ec-Sp revealed that the presence of a integrative conjugative element (ICE) results in increased adherence to human epithelial cells (P = 0.005). In contrast, sporadic non-Ec-Sp lacking the ICE had greater growth in vitro possibly resulting in improved fitness. In conclusion, non-Ec-Sp isolates from the classic lineage have evolved separately. They have spread globally, are well adapted to nasopharyngeal carriage and are able to coexist with Ec-Sp. Due to continued use of PCV, non-Ec-Sp may become more prevalent.Mahidol UniversityAgricultural and Biological SciencesBiochemistry, Genetics and Molecular BiologyGlobal phylogenomic analysis of nonencapsulated Streptococcus pneumoniae reveals a deep-branching classic lineage that is distinct from multiple sporadic lineagesArticleSCOPUS10.1093/gbe/evu263