R-evolution pneumo · The role of recombination in evolution and epidemiology of bacterial pathogen Streptococcus pneumoniae
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2013-04-01 → 2015-03-31
- Финансиране от ЕС
- 221 606 €
- Участници
- 1
- Схема
- MC-IEF
Линиите свързват координатора с партньорите.
Накратко на български
Бактерията Streptococcus pneumoniae и начинът, по който обменя генетичен материал, за да променя капсулата си или да става устойчива на антибиотици, са в центъра на анализа. Това помага да се разбере как патогенът избягва ваксините и се адаптира към медицинските терапии.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
The role of recombination in evolution and epidemiology of bacterial pathogen Streptococcus pneumoniae
Streptococcus pneumoniae is one of the deadliest bacterial pathogens, killing potentially as many as 1 million children worldwide each year. The pathogen is also one of the most diverse and recombinogenic bacteria known, making it a difficult target for vaccines and antimicrobial drugs. The aim of this project was to investigate the importance of the role of recombination in the evolution of the pathogen, particularly in the context of medical interventions. The research has several important findings. First, 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, leading to the hypothesis that the previously unobserved diversity may come from closely related bacteria. The research has compared most important groups of serotypes (serogroups) and found that they vary with respect to the rate of recombination and potential speed of adaptation. These results, which are currently written up for publication, suggest that polysaccharide vaccines may be selecting for novel serotypes in the future, thus highlighting the importance of further studies to investigate this issue further. Second, the results brought important insight into how recombination shapes the pneumococcal genome. Analysis of several pneumococcal lineages revealed that the evolution of the pathogen is driven by two different mechanisms, micro-recombination and macro-recombination. Of the two mechanisms, macro-recombination was found to be the mechanism associated with (a) serotype switching (alteration of serotype by recombination and thus a mechanism of vaccine evasion) and (b) with resistance to several major classes of antibiotics. Third, a novel approach of visualising genetic diversity of bacterial antigens was conceived, leading to an interesting new method to analyse population structure alignment free and identification of mosaic loci. To this end collaboration with researchers from Public Health England and University of Konstanz was commenced. The method will enable rapid analysis of signs of recombination in massive datasets in the future. Finally, a considerable effort went into promoting the issue of the emergence of antibiotic resistance in bacteria and increasing scepticism towards vaccines. In particular the researcher took part in FameLab, a public engagement competition to explain science in three minutes, gave public lectures and co-organised a summer school in epidemiology at Imperial College. These activities contributed towards increasing awareness of the overuse of antibiotics in Europe and promoting positive attitude towards vaccines, both in UK and Poland.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The aim of this project is to improve our understanding of the role of recombination (uptake and incorporation of foreign DNA) for the evolution and epidemiology of the major human bacterial pathogen Streptococcus pneumoniae, also known as the pneumococcus. There is an increasing appreciation of the public health significance of recombination in S. pneumoniae, where recombination has enabled major drug-resistant lineages to rapidly evade new conjugate vaccines. Here, I propose to investigate the role of different mechanisms of recombination in the context of (a) coevolution of the pathogen with the human immune system, (b) generation of novel antigenic diversity at the capsular locus, and (c) adaptation to clinical treatment by generation of novel bacterial lineages carrying multi-drug resistant genes and vaccine “escape” antigens. To do so, I will use an interdisciplinary approach of evolutionary microbiology, immunology, and epidemiology of infectious diseases. First, I will employ a generic evolutionary-epidemiological modelling approach to understand the population dynamic of recombination. Second, I will analyse newly available pneumococcal full-genome sequences to examine the link between recombination, immunity, vaccine, and drug-resistance in pneumococcus. The benefit of this research will be threefold. First, a better understanding of the role of recombination in coevolution with the human populations would be of benefit to the field of bacterial evolution and microbiology in general. Second, the approach outlined here can be applied to study recombination in other recombinogenic bacterial pathogens, like Neisseria meningitidis, Salmonella enterica or Helicobacter pylori. Finally, gaining further insight into the predicted long-term response against the current and future vaccines would help in the design of more effective forms of clinical interventions and help saving children’ lives.
Оригинален текст от CORDIS (на английски).
Участници
- IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз