Differences in genetic flux in invasive Streptococcus pneumoniae associated with bacteraemia and meningitis.

ABSTRACT

Background: Genetic flux, a crucial process of pneumococcal evolution, is an essential aspect of bacterial physiology during human pathogenesis. However, the role of these genetic changes and the selective forces that drive them is not fully understood. Elucidating the underlying selective forces that determine the magnitude and direction (gene gain or loss) of gene transfer is important for better understanding the pathogenesis process, and may also highlight potential therapeutic and diagnostic targets. Methods: Here, we leveraged data from high throughput genome sequencing and robust probabilistic models to discover the magnitude and likely direction of genetic flux events, but not the source, in 209 multi-lineage invasive pneumococcal genomes generated from blood (n = 147) and CSF (n = 62) isolates, associated with bacteremia and meningitis respectively. The Gain and Loss Mapping Engine (GLOOME) was used to infer gene gain and loss more accurately by taking into account differences in rates of gene gain and loss among gene families, as well as independent evolution within and across lineages. Results: Our results show the likely extent and direction of gene fluctuations at different niche, during pneumococcal pathogenesis, highlighting that evolutionary dynamics are important for tissue-specific host invasion and survival. Conclusion: These findings improve insights on evolutionary dynamics during invasive pneumococcal disease, and highlight potential diagnostic and therapeutic targets.