Dominant Role of Nucleotide Substitution in the Diversification of Serotype 3 Pneumococci over Decades and during a Single Infection

Abstract

Streptococcus pneumoniae of serotype 3 possess a mucoid capsule and cause disease associated with high mortality rates relative to other pneumococci. Phylogenetic analysis of a complete reference genome and 81 draft sequences from clonal complex 180, the predominant serotype 3 clone in much of the world, found most sampled isolates belonged to a clade affected by few diversifying recombinations. However, other isolates indicate significant genetic variation has accumulated over the clonal complex's entire history. Two closely related genomes, one from the blood and another from the cerebrospinal fluid, were obtained from a patient with meningitis. The pair differed in their behaviour in a mouse model of disease and in their susceptibility to antimicrobials, with at least some of these changes attributable to a mutation that up-regulated the patAB efflux pump. This indicates clinically important phenotypic variation can accumulate rapidly through small alterations to the genotype.

Variable recombination dynamics during the emergence, transmission and ‘disarming’ of a multidrug-resistant pneumococcal clone

“…Analysis with an alternative algorithm for detecting recombination produced similar results [see Additional file 2: Figure S1]. The reconstruction involved 3,955 point mutations, giving an estimate of the overall per site r/m (the ratio of base substitutions introduced by recombination relative to point mutations) of 14.9; this compares with a typical range from around 0.1 to more than 30 for common pneumococcal lineages [36,37]. However, it is clear that many of these events occurred within putative mobile genetic elements (MGEs) and were, therefore, unlikely to be the products of genetic transformation, but rather seemed to primarily represent the consequences of phage movement.…”

Genomic Analyses of Pneumococci from Children with Sickle Cell Disease Expose Host-Specific Bacterial Adaptations and Deficits in Current Interventions

“…Taken together, the data reveal that a high invasive disease risk remains in SCD children outside the scope of available conjugate vaccines. One important caveat is that even though strains were chosen for mouse challenge based on genetic similarity or capsule type, small alterations in genotype can confer strong alterations in virulence (Croucher et al, 2013b). Since the animal model suggested all isolates retained high virulence in the SCD model independent of capsule type or genetic background, we explored other factors that might more accurately define infection risk in this patient population.…”

The role of ZmpC in the clinical manifestation of invasive pneumococcal disease

“…This could mean that ZmpC has an effect on the airways that induces cough and as such facilitates transmission of the pneumococcal strain involved, taking for granted an increased risk of causing sepsis and IPD. Although this is mere speculation, multiple publications have pointed at a role for the pneumococcal genetic background in the risk of invasiveness (Browall et al, 2014;Brueggemann et al, 2003;Croucher et al, 2013;Hanage et al, 2005;Sandgren et al, 2004).…”