Putatively novel serotypes and the potential for reduced vaccine effectiveness: capsular locus diversity revealed among 5405 pneumococcal genomes

Abstract

The pneumococcus is a leading global pathogen and a key virulence factor possessed by the majority of pneumococci is an antigenic polysaccharide capsule (‘serotype’), which is encoded by the capsular (cps) locus. Approximately 100 different serotypes are known, but the extent of sequence diversity within the cps loci of individual serotypes is not well understood. Investigating serotype-specific sequence variation is crucial to the design of sequence-based serotyping methodology, understanding pneumococcal conjugate vaccine (PCV) effectiveness and the design of future PCVs. The availability of large genome datasets makes it possible to assess population-level variation among pneumococcal serotypes and in this study 5405 pneumococcal genomes were used to investigate cps locus diversity among 49 different serotypes. Pneumococci had been recovered between 1916 and 2014 from people of all ages living in 51 countries. Serotypes were deduced bioinformatically, cps locus sequences were extracted and variation was assessed within the cps locus, in the context of pneumococcal genetic lineages. Overall, cps locus sequence diversity varied markedly: low to moderate diversity was revealed among serogroups/types 1, 3, 7, 9, 11 and 22; whereas serogroups/types 6, 19, 23, 14, 15, 18, 33 and 35 displayed high diversity. Putative novel and/or hybrid cps loci were identified among all serogroups/types apart from 1, 3 and 9. This study demonstrated that cps locus sequence diversity varied widely between serogroups/types. Investigation of the biochemical structure of the polysaccharide capsule of major variants, particularly PCV-related serotypes and those that appear to be novel or hybrids, is warranted.

Deep genome annotation of the opportunistic human pathogenStreptococcus pneumoniaeD39

“…We further unveiled the mosaic nature of pneumococcal histidine triad proteins, and especially vaccine candidate PhtD, variation of which is facilitated both by the aforementioned chromosomal inversion and more local recombination events. This observation expands the set of previously identified highly variable pneumococcal antigens (76,77). Figure 5).…”

Transcriptome Remodeling of Acinetobacter baumannii during Infection and Treatment

“…For example, the csu region has been altered multiple independent times in A. baumannii (13, 15) and we observed both increased and decreased expression relative to that in isogenic isolates from several patients. In an analysis of IS locations in over 1,000 A. baumannii genomes, the 5-kbp region containing the csu genes had over 90 independent insertion events, a density approximately three times higher than that in any other 5-kb region of the genome (12). This provides compelling evidence that alteration of this region is under selection.…”

“…Briefly, genomic reads were mapped to the first isolate from the series and SNVs were called with FreeBayes (arXiv:1207.3907v2). Insertion sequence events were identified with ISseeker (12). Clade level genetic differences were identified by assembly-based SNV calling in kSNP (51) and verified manually to confirm that variants were isolate, patient, or clade specific by using blast queries with all of the available A. baumannii genomes in the UHHS population (11, 13).…”

“…Here we explore how these mutations impact the transcriptome and whether there is evidence for convergence toward a common transcriptional profile in clinical A. baumannii strains. Population level genomic analysis of A. baumannii strains also reveals a dynamic genome modified by mutations, IS events, deletions, and gene acquisitions (12, 13). Therefore, we also assessed how population level genetic variation alters the transcriptome across major lineages.…”

Frequent recombination of pneumococcal capsule highlights future risks of emergence of novel serotypes

“…This is not surprising as the pneumococcus is known to undergo frequent recombination (Feil et al, 2000;Henriques-Normark et al, 2008;Vos and Didelot, 2009), and the capsular locus was shown to be a recombination hotspot (Croucher et al, 2011;Chewapreecha et al, 2014). Furthermore, we know from previous studies that the extent of within-serotype diversity is under-appreciated, with many hybrid serotypes circulating in the population (Salter et al, 2012;van Tonder et al, 2016). However, the evolutionary dynamics, and hence the full adaptive potential of pneumococcal capsular polysaccharides, are not well understood.…”