Mostowy Rafal, Croucher Nicholas J, Hanage William P, Harris Simon R, Bentley Stephen, Fraser Christophe
Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Campus, London, United Kingdom.
Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Campus, London, United Kingdom; Center for Communicable Disease Dynamics, Harvard School of Public Health, Boston, Massachusetts, United States of America; The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
PLoS Genet. 2014 May 1;10(5):e1004300. doi: 10.1371/journal.pgen.1004300. eCollection 2014 May.
The bacterium Streptococcus pneumoniae (pneumococcus) is one of the most important human bacterial pathogens, and a leading cause of morbidity and mortality worldwide. The pneumococcus is also known for undergoing extensive homologous recombination via transformation with exogenous DNA. It has been shown that recombination has a major impact on the evolution of the pathogen, including acquisition of antibiotic resistance and serotype-switching. Nevertheless, the mechanism and the rates of recombination in an epidemiological context remain poorly understood. Here, we proposed several mathematical models to describe the rate and size of recombination in the evolutionary history of two very distinct pneumococcal lineages, PMEN1 and CC180. We found that, in both lineages, the process of homologous recombination was best described by a heterogeneous model of recombination with single, short, frequent replacements, which we call micro-recombinations, and rarer, multi-fragment, saltational replacements, which we call macro-recombinations. Macro-recombination was associated with major phenotypic changes, including serotype-switching events, and thus was a major driver of the diversification of the pathogen. We critically evaluate biological and epidemiological processes that could give rise to the micro-recombination and macro-recombination processes.
肺炎链球菌是最重要的人类细菌病原体之一，也是全球发病和死亡的主要原因。肺炎链球菌还因通过与外源DNA转化进行广泛的同源重组而闻名。研究表明，重组对病原体的进化有重大影响，包括获得抗生素耐药性和血清型转换。然而，在流行病学背景下，重组的机制和速率仍知之甚少。在此，我们提出了几个数学模型来描述两个非常不同的肺炎链球菌谱系PMEN1和CC180进化历史中的重组速率和大小。我们发现，在这两个谱系中，同源重组过程最好用一种异质重组模型来描述，即单个、短片段、频繁的替换，我们称之为微重组，以及罕见的、多片段、跳跃式替换，我们称之为宏重组。宏重组与主要的表型变化有关，包括血清型转换事件，因此是病原体多样化的主要驱动力。我们批判性地评估了可能导致微重组和宏重组过程的生物学和流行病学过程。
