Dominant role of nucleotide substitution in the diversification of serotype 3 pneumococci over decades and during a single infection.
Dominant role of nucleotide substitution in the diversification of serotype 3 pneumococci over decades and during a single infection.
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DOI：
10.1371/journal.pgen.1003868
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Bentley SD
中科院分区：
文献类型：
--
作者：
Croucher NJ;Mitchell AM;Gould KA;Inverarity D;Barquist L;Feltwell T;Fookes MC;Harris SR;Dordel J;Salter SJ;Browall S;Zemlickova H;Parkhill J;Normark S;Henriques-Normark B;Hinds J;Mitchell TJ;Bentley SD
血清型3的肺炎链球菌具有粘液样荚膜，并且相对于其它肺炎球菌引起与高死亡率相关的疾病。系统发育分析的一个完整的参考基因组和81个草图序列的克隆复合体180，在世界上大部分地区的主要血清型3克隆，发现大多数采样菌株属于一个分支的影响，少数多样化重组。然而，其他分离物表明，在克隆复合体的整个历史中积累了显着的遗传变异。两个密切相关的基因组，一个来自血液，另一个来自脑脊液，从脑膜炎患者中获得。这对在小鼠疾病模型中的行为和对抗菌剂的敏感性不同，其中至少有一些变化可归因于上调patAB外排泵的突变。这表明临床上重要的表型变异可以通过基因型的微小改变迅速积累。 肺炎链球菌（“肺炎球菌”）是一种常见于人鼻咽部的无症状细菌，是肺炎、菌血症和脑膜炎等疾病的常见病因。一些菌株已被发现与其他细菌以高速率交换DNA。然而，血清3型肺炎球菌是不寻常的，既没有表现出太多的遗传变异，并导致疾病的相对较高的死亡率。在这里，我们使用全基因组测序来检测82个血清3型肺炎球菌，发现大多数人群的变异积累非常缓慢。然而，比较来自单一病例的两个分离株，发现在短时间内发生了少量突变。这些导致了几个基因活性的差异，包括两个编码药物外排泵的基因。发现这对分离株在对不同抗菌化合物的耐受性和它们在小鼠疾病模型中的行为方面存在差异。然而，将导致耐药性变化的突变转移到远缘肺炎球菌中未能完全复制其他行为变化，这表明很难解释不同细菌物种的不同菌株中突变的影响。
Streptococcus pneumoniae of serotype 3 possess a mucoid capsule and cause disease associated with high mortality rates relative to other pneumococci. Phylogenetic analysis of a complete reference genome and 81 draft sequences from clonal complex 180, the predominant serotype 3 clone in much of the world, found most sampled isolates belonged to a clade affected by few diversifying recombinations. However, other isolates indicate significant genetic variation has accumulated over the clonal complex's entire history. Two closely related genomes, one from the blood and another from the cerebrospinal fluid, were obtained from a patient with meningitis. The pair differed in their behaviour in a mouse model of disease and in their susceptibility to antimicrobials, with at least some of these changes attributable to a mutation that up-regulated the patAB efflux pump. This indicates clinically important phenotypic variation can accumulate rapidly through small alterations to the genotype. Streptococcus pneumoniae (‘the pneumococcus’) is a bacterium commonly found asymptomatically in the human nasopharynx that represents a common cause of diseases such as pneumonia, bacteraemia and meningitis. Some strains have been found to exchange DNA with other bacteria at a high rate. However, serotype 3 pneumococci are unusual both in not exhibiting much genetic variation and causing disease with a comparatively high relative rate of mortality. Here we used whole genome sequencing to characterise 82 serotype 3 pneumococci, finding that the majority of the population accumulate variation very slowly. However, comparing two isolates from a single case of disease revealed a small number of mutations had occurred over a short period of time. These resulted in differences in the activity of several genes, including two encoding a drug efflux pump. The pair of isolates was found to differ in their tolerance of different antimicrobial compounds and their behaviour in a mouse model of disease. However, moving the mutation that caused the change in resistance into a distantly-related pneumococcus failed to fully replicate the other changes in behaviour, which indicates that interpretation of the impact of mutations in different strains of diverse bacterial species will be difficult.
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影响因子：
4.9
作者：
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通讯作者：
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通讯作者：
Denamur E
影响因子：
6.7
作者：
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通讯作者：
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