Hilty, MarkusMarkusHilty0000-0002-2418-6474Wüthrich, DanielDanielWüthrichSalter, Susannah JSusannah JSalterEngel, Hans JürgHans JürgEngelCampbell, SamuelSamuelCampbellSá-Leão, RaquelRaquelSá-Leãode Lencastre, HermíniaHermíniade LencastreHermans, PeterPeterHermansSadowy, EwaEwaSadowyTurner, PaulPaulTurnerChewapreecha, ClaireClaireChewapreechaDiggle, MathewMathewDigglePluschke, GerdGerdPluschkeMcGee, LesleyLesleyMcGeeEser, Ozgen KöseoğluOzgen KöseoğluEserLow, Donald EDonald ELowSmith-Vaughan, HeidiHeidiSmith-VaughanEndimiani, AndreaAndreaEndimiani0000-0003-3186-5421Küffer, MarianneMarianneKüfferDupasquier, MélanieMélanieDupasquierBeaudoing, EmmanuelEmmanuelBeaudoingWeber, JohannJohannWeberBruggmann, RémyRémyBruggmannHanage, William PWilliam PHanageParkhill, JulianJulianParkhillHathaway, Lucy JaneLucy JaneHathaway0000-0002-5361-5397Mühlemann, KathrinKathrinMühlemannBentley, Stephen DStephen DBentley2024-10-232024-10-232014-12-04https://boris-portal.unibe.ch/handle/20.500.12422/127845The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated Streptococcus 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 non-susceptiblity 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 multi-locus sequences types ST344 (n=39) and ST448 (n=40). All ST344 and nine ST448 isolates had high non-susceptiblity 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 pneumococcal conjugate vaccines, Non-Ec-Sp may become more prevalent.enPneumococcal isolatesantibiotic non-susceptibilitycomparative genomicsintegrative conjugative elements (ICEs)whole genome sequencing500 - Science::570 - Life sciences; biology600 - Technology::610 - Medicine & healtharticle10.7892/boris.609092548068610.1093/gbe/evu263