Pneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models.
Pneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models.
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DOI：
10.1093/molbev/msab018
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发表时间：
2021-05-19
影响因子：
10.7
通讯作者：
Neill DR
中科院分区：
文献类型：
--
作者：
Green AE;Howarth D;Chaguza C;Echlin H;Langendonk RF;Munro C;Barton TE;Hinton JCD;Bentley SD;Rosch JW;Neill DR
肺炎链球菌是人类鼻咽部的共生菌，也是呼吸道和侵袭性疾病的主要原因。我们在一个实验系统中研究了鼻咽和肺部内肺炎球菌的适应和进化，其中与传播相关的选择压力被消除。这是通过在鼻咽携带或肺炎小鼠模型中分别连续传代肺炎球菌来实现的。传代的肺炎球菌成为更有效的呼吸道定植者，我们观察到了几个潜在平行进化的例子。细胞壁修饰糖基转移酶 LafA 在肺传代过程中受到强烈选择，而表面表达的肺炎球菌疫苗抗原基因 pvaA 和 3-磷酸甘油脱氢酶基因 gpsA 是鼻咽传代肺炎球菌中常见的突变目标。这些突变在通过实验室琼脂连续传代单独进化的肺炎球菌中没有发现。我们关注 gpsA，其中相同的单核苷酸多态性出现在两个独立进化的鼻咽传代谱系中。我们描述了该基因在鼻咽运输中的新作用，并表明所鉴定的单核苷酸变化赋予了对氧化应激的抵抗力并增强了鼻咽定植潜力。我们证明 gpsA 的多态性在人类殖民过程中出现并保留。这些发现强调了宿主内部环境条件如何决定细菌进化的轨迹。肺炎球菌谱系的相对侵袭性或攻击率可能由对细菌适应性做出特定生态位贡献的基因来定义。动物感染模型的实验进化是研究病原体毒力和定植因子在不同宿主生态位中所发挥的相对作用的有力工具。
Streptococcus pneumoniae is a commensal of the human nasopharynx and a major cause of respiratory and invasive disease. We examined adaptation and evolution of pneumococcus, within nasopharynx and lungs, in an experimental system where the selective pressures associated with transmission were removed. This was achieved by serial passage of pneumococci, separately, in mouse models of nasopharyngeal carriage or pneumonia. Passaged pneumococci became more effective colonizers of the respiratory tract and we observed several examples of potential parallel evolution. The cell wall-modifying glycosyltransferase LafA was under strong selection during lung passage, whereas the surface expressed pneumococcal vaccine antigen gene pvaA and the glycerol-3-phosphate dehydrogenase gene gpsA were frequent targets of mutation in nasopharynx-passaged pneumococci. These mutations were not identified in pneumococci that were separately evolved by serial passage on laboratory agar. We focused on gpsA, in which the same single nucleotide polymorphism arose in two independently evolved nasopharynx-passaged lineages. We describe a new role for this gene in nasopharyngeal carriage and show that the identified single nucleotide change confers resistance to oxidative stress and enhanced nasopharyngeal colonization potential. We demonstrate that polymorphisms in gpsA arise and are retained during human colonization. These findings highlight how within-host environmental conditions can determine trajectories of bacterial evolution. Relative invasiveness or attack rate of pneumococcal lineages may be defined by genes that make niche-specific contributions to bacterial fitness. Experimental evolution in animal infection models is a powerful tool to investigate the relative roles played by pathogen virulence and colonization factors within different host niches.
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影响因子：
3.9
作者：
Connor TR;Loman NJ;Thompson S;Smith A;Southgate J;Poplawski R;Bull MJ;Richardson E;Ismail M;Thompson SE;Kitchen C;Guest M;Bakke M;Sheppard SK;Pallen MJ
通讯作者：
Pallen MJ
Biopython：用于计算分子生物学和生物信息学的免费 Python 工具。
DOI：
10.1093/bioinformatics/btp163
发表时间：
2009-06-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Cock PJ;Antao T;Chang JT;Chapman BA;Cox CJ;Dalke A;Friedberg I;Hamelryck T;Kauff F;Wilczynski B;de Hoon MJ
通讯作者：
de Hoon MJ
影响因子：
3.1
作者：
BERRY, AM;YOTHER, J;PATON, JC
通讯作者：
PATON, JC
影响因子：
6.4
作者：
Jefferies, Johanna M. C.;Johnston, Calum H. G.;Mitchell, Tim J.
通讯作者：
Mitchell, Tim J.
影响因子：
3.1
作者：
Kadioglu, A;Gingles, NA;Andrew, PW
通讯作者：
Andrew, PW