Puzzling Over the Pneumococcal Pangenome

Abstract

The Gram positive bacterium Streptococcus pneumoniae (pneumococcus) is a major human pathogen. It is a common colonizer of the human host, and in the nasopharynx, sinus, and middle ear it survives as a biofilm. This mode of growth is optimal for multi-strain colonization and genetic exchange. Over the last decades, the far-reaching use of antibiotics and the widespread implementation of pneumococcal multivalent conjugate vaccines have posed considerable selective pressure on pneumococci. This scenario provides an exceptional opportunity to study the evolution of the pangenome of a clinically important bacterium, and has the potential to serve as a case study for other species. The goal of this review is to highlight key findings in the studies of pneumococcal genomic diversity and plasticity.

Keywords: Streptococcus pneumoniae (pneumococcus); antibiotics; competence; genomic diversity; genomic plasticity; horizontal gene transfer; pangenome; vaccine.

FIGURE 1

Chart illustrates pneumococcal genomic diversity. Distribution of orthologous clusters in a single isolate (inner circle), and the pangenome (outer circle). The core orthologous clusters are shared across all pneumococcal strains (red), and the accessory orthologous clusters are those not encoded in all strains, but instead unevenly distributed across isolates of this species (blue). The pangenome is the comprehensive set of all the orthologous clusters in the species.

FIGURE 2

Schematic of pneumococcal genomic plasticity. Schematic is build on a phylogenetic tree of a subset of streptococcal species (adapted from Antic et al., 2017). Arrows indicate gene transfer events discussed in this article. (A) Pneumococcal genomes, shaped by recombination across strains. The rates of gene exchange vary across lineages. Non-encapsulated strains display high rates of transfer, and may serve as recombination highways. The PMEN1 lineage (type 81) has impacted the genomes of multiple lineages as a common gene donor. The PMEN31 lineage (serotype 3 lineage from clonal complex 180) has relatively stable genomes. (B) A distinct phyletic branch captures strain differentiation. It is composed of the classical non-typable strains, which colonize the nasopharynx and can cause conjunctivitis. Gene exchange between this branch and all other pneumococci may prevent speciation. (C) Gene transfer between S. pneumoniae and S. mitis has played a critical role in penicillin resistance via formation of mosaic PBPs. (D) Gene transfer between S. suis and S. pneumoniae, illustrated by the acquisition of an adhesin by pneumococci.