The surrounding capsule of @entity328 has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines ( @entity1485 ). However, nonencapsulated @entity2260 (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 @entity2260 (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 b-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 @entity1 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 @entity1 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 @entity1485 , non-Ec-Sp may become more prevalent.

Global Phylogenomic Analysis of Nonencapsulated XXXX Reveals a Deep-Branching Classic Lineage That Is Distinct from Multiple Sporadic Lineages.

@entity1 :: ('9606', 'Species') :: ['human'] @entity2260 :: ('2104', 'Species') :: ['S. pneumoniae'] @entity328 :: ('1313', 'Species') :: ['Streptococcus pneumoniae'] @entity1485 :: ('158372', 'Species') :: ['PCV']
@entity328 :: (1313,Species) :: ['Streptococcus pneumoniae']
