Recombination mechanisms and coevolution in human pathogens
The R-EVOLUTION PNEUMO (The role of recombination in evolution and epidemiology of bacterial pathogen Streptococcus pneumoniae) project increased understanding of the role of recombination of the major human bacterial pathogen Streptococcus pneumoniae, also known as pneumococcus. An interdisciplinary approach was applied based on evolutionary microbiology, immunology and epidemiology of infectious diseases. Generic evolutionary epidemiological models were employed to understand the population dynamics of recombination. In addition, pneumococcal full-genome sequences were used to determine the links between recombination, immunity, vaccination and drug resistance. Genetic analysis of vaccine targets - capsular polysaccharides - revealed that these loci actively evolve by recombination leading to the emergence of novel types. Many of the recombinations found came from an unknown source. This led to the hypothesis that the previously unobserved diversity may come from closely related bacteria. Comparison of the most significant groups of serotypes revealed that they vary with respect to the rate of recombination and potential speed of adaptation. This suggests that polysaccharide vaccines may select for novel serotypes in the future, underlining the importance of further research in this area. Analysis of several pneumococcal lineages showed that the evolution of the pathogen is driven by two different mechanisms, micro-recombination and macro-recombination. Macro-recombination was found to be the mechanism associated with serotype switching (alteration of serotype by recombination and thus a mechanism of vaccine evasion) and with resistance to several major classes of antibiotics. A novel approach was also used to visualise genetic diversity of bacterial antigens. The result was a new method for analysing population structure and identifying mosaic loci (mosaicism being the expression of genes in some but not all the cells of a given individual). This will enable the rapid analysis of signs of recombination in massive datasets in the future. R-EVOLUTION PNEUMO will provide a clearer understanding of the role of S. pneumoniae recombination in coevolution with human populations. In addition the project’s findings can be applied to other pathogens such as Neisseria meningitidis, Salmonella enterica and Helicobacter pylori. The insights achieved into the predicted long-term response against the current and future vaccines will help in the design of more effective treatments and help save patients’ lives.
Keywords
Recombination, Streptococcus pneumoniae, coevolution, human immune system, full-genome sequence, capsular polysaccharides, pneumococcal lineages, mosaic loci
