Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella.
Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella.
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DOI：
10.1073/pnas.1714718115
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发表时间：
2018-03-13
影响因子：
11.1
通讯作者：
Hinton JCD
中科院分区：
文献类型：
--
作者：
Hammarlöf DL;Kröger C;Owen SV;Canals R;Lacharme-Lora L;Wenner N;Schager AE;Wells TJ;Henderson IR;Wigley P;Hokamp K;Feasey NA;Gordon MA;Hinton JCD
侵袭性非伤寒沙门氏菌病是一种主要的和以前被忽视的热带疾病，估计每年在非洲造成390，000人死亡，主要由称为ST 313的鼠伤寒沙门氏菌变体引起。尽管有超过100，000个沙门氏菌基因组可用，但已证明将单个SNP与这种危险细菌的致病性状相关联具有挑战性。在这里，我们使用了转录组学的策略，以确定一个启动子区域的单核苷酸的变化，负责非洲S。鼠伤寒。我们的研究结果表明，细菌基因组的非编码核苷酸可以对感染性疾病的发病机制产生深远的影响。肠道沙门氏菌血清型鼠伤寒沙门氏菌ST 313是一种相对较新出现的序列类型，它在撒哈拉以南非洲地区引起了毁灭性的血流感染流行病。对数百种沙门氏菌基因组的分析表明，ST 313与沙门氏菌的ST 19群密切相关。在全世界引起肠胃炎的鼠伤寒。ST 313和ST 19的核心基因组仅相差1,000个SNP。我们假设，区分非洲沙门氏菌和ST 19的表型差异是由某些直接调节毒力基因转录的SNP引起的。在这里，我们确定了ST 313菌株D23580的3，597个转录起始位点，并搜索了与沙门氏菌发病机制相关的基因表达特征。我们在pgtE基因的启动子中鉴定了一个SNP，该SNP导致非洲链球菌中PgtE毒力因子的高表达。鼠伤寒沙门氏菌，增加人补体B因子组分的降解，有助于血清抗性，并在鸡感染模型中调节毒力。我们认为非洲S.鼠伤寒沙门氏菌ST 313在人类感染期间促进细菌存活和传播。我们发现一个基因外SNP的功能作用表明，用于推断细菌病原体毒力进化的方法应包括关注基因组的非编码区。
Invasive nontyphoidal Salmonella disease is a major and previously neglected tropical disease responsible for an estimated ∼390,000 deaths per year in Africa, largely caused by a variant of Salmonella Typhimurium called ST313. Despite the availability of >100,000 Salmonella genomes, it has proven challenging to associate individual SNPs with pathogenic traits of this dangerous bacterium. Here, we used a transcriptomic strategy to identify a single-nucleotide change in a promoter region responsible for crucial phenotypic differences of African S. Typhimurium. Our findings show that a noncoding nucleotide of the bacterial genome can have a profound effect upon the pathogenesis of infectious disease. Salmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely related to the ST19 group of S. Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by only ∼1,000 SNPs. We hypothesized that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites of the ST313 strain D23580, and searched for a gene-expression signature linked to pathogenesis of Salmonella. We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance, and modulated virulence in the chicken infection model. We propose that high levels of PgtE expression by African S. Typhimurium ST313 promote bacterial survival and dissemination during human infection. Our finding of a functional role for an extragenic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on noncoding regions of the genome.
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DOI：
10.1093/bioinformatics/btp347
发表时间：
2009-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Assefa S;Keane TM;Otto TD;Newbold C;Berriman M
通讯作者：
Berriman M
影响因子：
168.9
作者：
Feasey, Nicholas A.;Dougan, Gordon;Kingsley, Robert A.;Heyderman, Robert S.;Gordon, Melita A.
通讯作者：
Gordon, Melita A.
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
影响因子：
2.2
作者：
Goh, Yun Shan;MacLennan, Calman A.
通讯作者：
MacLennan, Calman A.
影响因子：
30.3
作者：
Kroeger, Carsten;Colgan, Aoife;Hinton, Jay C. D.
通讯作者：
Hinton, Jay C. D.