Abstract
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.
Highlights
Streptococcus pneumoniae is an important human pathogen usually surrounded by a polysaccharide capsule which is considered to be a major virulence factor
Assembled genomes were annotated revealing a total of 1,148 clusters of orthologous groups (COGs) which were present in all 131 non-encapsulated S. pneumoniae (Ec-surface proteins (Sp)) genomes and represent the non-Ec-Sp core genome
Global collection of 44 Ec-Sp were added to the data set reducing the number of core COGs to 858 (Donati et al 2010)
Summary
Streptococcus pneumoniae is an important human pathogen usually surrounded by a polysaccharide capsule which is considered to be a major virulence factor. Generally considered less virulent than encapsulated strains, non-Ec-Sp are isolated from sterile sites and make up 10% of those isolated from the nasopharynx (Finland and Barnes 1977; Carvalho et al 2003). Some non-Ec-Sp clones have been repeatedly isolated worldwide, sequence types (STs) ST344 and ST448 indicating intercontinental spread that may reflect an adaptive advantage in transmission. These types are associated with outbreaks of conjunctivitis (Martin et al 2003; Porat et al 2006). Non-Ec-Sp may be repositories of antibiotic resistance genes which could be transferred to encapsulated pneumococci (Hauser et al 2004; Chewapreecha et al 2014)
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