A new perspective on Listeria monocytogenes evolution.

A new perspective on Listeria monocytogenes evolution.
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DOI:
10.1371/journal.ppat.1000146
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发表时间:
2008-09-05
期刊:
影响因子:
6.7
通讯作者:
Brisse, Sylvain
Brisse, Sylvain
中科院分区:
医学1区
文献类型:
--
作者:
Ragon, Marie;Wirth, Thierry;Hollandt, Florian;Lavenir, Rachel;Lecuit, Marc;Le Monnier, Alban;Brisse, Sylvain

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单核细胞增生李斯特氏菌是细胞微生物学和宿主-病原体相互作用研究的模型生物,也是环境中广泛分布的重要食源性病原体,因此代表了研究毒力进化的有吸引力的模型。通过对 360 个代表性分离株中 7 个管家基因(3,288 个核苷酸)的内部部分进行测序,确定了单核细胞增生李斯特菌的系统发育结构。 126 种公开的序列类型中的 58 种被分为 7 个界限明确的克隆复合体(克隆),几乎占临床分离株的 75%。每个克隆都有一个独特的或显性的血清型(克隆1、2和4为4b,克隆3和5为1/2b,克隆7为1/2a,克隆9为1/2c),克隆与人类李斯特菌病的临床形式没有关联。同源重组极其有限(核苷酸的 r/m<1),这意味着多位点基因型随着时间的推移具有长期的遗传稳定性。基于 438 个 SNP 的贝叶斯分析恢复了三个先前定义的谱系,以及一个未分类的混合血统分离株。血清型的系统发育分布表明,血清型4b从1/2b(可能是谱系I的祖先血清型)进化一次。血清型1/2c从1/2a衍生一次,参考菌株EGDe(1/2a)可能代表中间进化状态。与管家基因相反,毒力因子内蛋白(InlA)通过局部重组进化,形成镶嵌模式,趋同进化表明自然选择导致 InlA 蛋白截短。这项工作为未来单增李斯特菌流行病学、生态学和毒力的研究提供了参考进化框架。 单核细胞增多性李斯特菌是一种通过受污染的食物传播的病原体,可导致动物和人类的严重感染,包括脑膜炎和流产。众所周知,这种病原体存在许多不同的菌株,它们的毒力和流行潜力各不相同。不幸的是,目前还没有菌株的标准定义,也没有对其进化的全面概述。为了解决李斯特菌病控制的这些严重限制并提高对毒力如何演变的了解,我们使用基于序列的基因分型方法对大量分离株进行了表征。因此,我们能够精确地识别单核细胞增生李斯特氏菌最常见的克隆,即源自单一祖先细菌的分离群,现在可以对其进行进一步表征,以用于诊断目的并确定其精确的生态学和毒力潜力。我们还确定了这些克隆如何从其共同祖先进化而来,以及它们获得表型特征(例如抗原结构)的进化历史。最后,我们发现一些特定菌株往往会失去在人类感染中发挥关键作用的毒力因子。这是病原体毒力降低的进化的罕见例子,这种现象背后的选择性力量的发现可能具有重要的流行病学和生物学意义。
Listeria monocytogenes is a model organism for cellular microbiology and host–pathogen interaction studies and an important food-borne pathogen widespread in the environment, thus representing an attractive model to study the evolution of virulence. The phylogenetic structure of L. monocytogenes was determined by sequencing internal portions of seven housekeeping genes (3,288 nucleotides) in 360 representative isolates. Fifty-eight of the 126 disclosed sequence types were grouped into seven well-demarcated clonal complexes (clones) that comprised almost 75% of clinical isolates. Each clone had a unique or dominant serotype (4b for clones 1, 2 and 4, 1/2b for clones 3 and 5, 1/2a for clone 7, and 1/2c for clone 9), with no association of clones with clinical forms of human listeriosis. Homologous recombination was extremely limited (r/m<1 for nucleotides), implying long-term genetic stability of multilocus genotypes over time. Bayesian analysis based on 438 SNPs recovered the three previously defined lineages, plus one unclassified isolate of mixed ancestry. The phylogenetic distribution of serotypes indicated that serotype 4b evolved once from 1/2b, the likely ancestral serotype of lineage I. Serotype 1/2c derived once from 1/2a, with reference strain EGDe (1/2a) likely representing an intermediate evolutionary state. In contrast to housekeeping genes, the virulence factor internalin (InlA) evolved by localized recombination resulting in a mosaic pattern, with convergent evolution indicative of natural selection towards a truncation of InlA protein. This work provides a reference evolutionary framework for future studies on L. monocytogenes epidemiology, ecology, and virulence. Listeria monocytogenes is a pathogen transmitted through contaminated food and is responsible for severe infections, including meningitis and abortion in animals and humans. It is known that many distinct strains of this pathogen exist, and that they differ in their virulence and epidemic potential. Unfortunately, there is currently no standard definition of strains and no comprehensive overview of their evolution. To tackle these serious limitations to the control of listeriosis and to improve knowledge of how virulence evolves, we characterized a large collection of isolates with sequence-based genotyping methods. We were thus able to identify precisely the most prevalent clones of L. monocytogenes, i.e., groups of isolates that descend from a single ancestral bacterium, which can now be characterized further for diagnostic purposes and determination of their precise ecology and virulence potential. We also determined how these clones evolved from their common ancestor and the evolutionary history by which they acquired their phenotypic characteristics, such as antigenic structures. Finally, we show that some particular strains tend to lose a virulence factor that plays a crucial role in infection in humans. This is a rare example of evolution towards reduced virulence of pathogens, and the discovery of the selective forces behind this phenomenon may have important epidemiological and biological implications.
DOI: 10.1534/genetics.106.063305
发表时间: 2007-03-01
期刊: GENETICS
影响因子: 3.3
作者:
Didelot, Xavier;Falush, Daniel
通讯作者: Falush, Daniel
DOI: 10.1128/jcm.01873-07
发表时间: 2008-04-01
影响因子: 9.4
作者:
Chen, Yi;Knabel, Stephen J.
通讯作者: Knabel, Stephen J.
DOI: 10.1128/jcm.32.12.2936-2943.1994
发表时间: 1994-12-01
影响因子: 9.4
作者:
GRAVES, LM;SWAMINATHAN, B;SCHUCHAT, A
通讯作者: SCHUCHAT, A
DOI: 10.1098/rstb.2006.1925
发表时间: 2006-11-29
期刊: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子: --
作者:
Falush D;Torpdahl M;Didelot X;Conrad DF;Wilson DJ;Achtman M
通讯作者: Achtman M
DOI: 10.1128/jb.173.22.7257-7268.1991
发表时间: 1991-11-01
影响因子: 3.2
作者:
DYKHUIZEN, DE;GREEN, L
通讯作者: GREEN, L