Comparative Genomic Analysis and In Vivo Modeling of Streptococcus pneumoniae ST3081 and ST618 Isolates Reveal Key Genetic and Phenotypic Differences Contributing to Clonal Replacement of Serotype 1 in The Gambia.
Comparative Genomic Analysis and In Vivo Modeling of Streptococcus pneumoniae ST3081 and ST618 Isolates Reveal Key Genetic and Phenotypic Differences Contributing to Clonal Replacement of Serotype 1 in The Gambia.
复制标题
DOI：
10.1093/infdis/jix472
复制
发表时间：
2017-12-05
期刊：
影响因子：
--
通讯作者：
Kadioglu A
中科院分区：
文献类型：
--
作者：
Bricio-Moreno L;Ebruke C;Chaguza C;Cornick J;Kwambana-Adams B;Yang M;Mackenzie G;Wren BW;Everett D;Antonio M;Kadioglu A
在这项研究中，我们提供了重要的证据表明，在冈比亚的肺炎球菌血清型1序列类型的流行病学的变化可能是一个直接的后果，随着时间的推移，在毒力和增加的能力殖民主机的差异。 肺炎链球菌血清型1是西非侵袭性肺炎球菌病（IPD）的主要原因之一，其中ST 618是冈比亚IPD的主要原因。然而，最近，观察到克隆替代的罕见实例，其中血清型1的ST 3081克隆替代占优势的ST 618克隆作为IPD的主要原因。在目前的研究中，我们试图找到这种不寻常的更换事件的原因。使用全基因组序列分析和临床相关的体内感染模型，我们确定了新出现的ST 3081克隆的独特的遗传和表型特征。我们发现，ST 3081在侵袭性肺炎模型中比ST 618毒力更强，并且在鼻咽携带过程中以比ST 618更高的密度携带。我们还观察到序列类型特异性的辅助基因和独特的序列类型特异性的固定突变的肺炎球菌毒素肺炎球菌溶血素，这是与增加溶血活性ST 3081，并可能有助于增加在这个克隆的毒力。我们的研究提供的证据表明，在相同的血清型1克隆复合物，生物学特性显着不同的克隆在毒力和宿主侵袭力方面，这些差异可能是基因组内的关键遗传差异的结果。
In this study we provide important evidence to show that changes in the epidemiology of pneumococcal serotype 1 sequence types in The Gambia may be a direct consequence of differences in virulence and increased ability to colonize hosts over time. Streptococcus pneumoniae serotype 1 is one of the leading causes of invasive pneumococcal disease (IPD) in West Africa, with ST618 being the dominant cause of IPD in The Gambia. Recently however, a rare example of clonal replacement was observed, where the ST3081 clone of serotype 1 replaced the predominant ST618 clone as the main cause of IPD. In the current study, we sought to find the reasons for this unusual replacement event. Using whole-genome sequence analysis and clinically relevant models of in vivo infection, we identified distinct genetic and phenotypic characteristics of the emerging ST3081 clone. We show that ST3081 is significantly more virulent than ST618 in models of invasive pneumonia, and is carried at higher densities than ST618 during nasopharyngeal carriage. We also observe sequence type–specific accessory genes and a unique sequence type–specific fixed mutation in the pneumococcal toxin pneumolysin, which is associated with increased hemolytic activity in ST3081 and may contribute to increased virulence in this clone. Our study provides evidence that, within the same serotype 1 clonal complex, biological properties differ significantly from one clone to another in terms of virulence and host invasiveness, and that these differences may be the result of key genetic differences within the genome.
登录
查看更多内容
影响因子：
6.4
作者：
Jin, Ping;Kong, Fanrong;Gilbert, Gwendolyn L.
通讯作者：
Gilbert, Gwendolyn L.
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：
Kadioglu, A;Gingles, NA;Andrew, PW
通讯作者：
Andrew, PW
影响因子：
3.1
作者：
BERRY, AM;ALEXANDER, JE;PATON, JC
通讯作者：
PATON, JC
影响因子：
3.1
作者：
Kadioglu, A;Taylor, S;Andrew, PW
通讯作者：
Andrew, PW