Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies.
Bacterial Factors Associated with Lethal Outcome of Enteropathogenic Escherichia coli Infection: Genomic Case-Control Studies.
复制标题
DOI：
10.1371/journal.pntd.0003791
复制
发表时间：
2015-05
影响因子：
3.8
通讯作者：
Nataro JP
中科院分区：
文献类型：
--
作者：
Donnenberg MS;Hazen TH;Farag TH;Panchalingam S;Antonio M;Hossain A;Mandomando I;Ochieng JB;Ramamurthy T;Tamboura B;Zaidi A;Levine MM;Kotloff K;Rasko DA;Nataro JP
在全球肠道多中心研究(GEMS)中，典型的肠源性大肠埃希菌(TEPEC)菌株与死亡率有关。TEPEC菌株的遗传差异可能是临床结果的一些差异的基础。我们制作了来自GEMS致死性感染(LIS)的所有可用的tEPEC菌株以及来自患有非致死性症状感染(NSI)和无症状感染(AIS)的GEMS受试者的紧密匹配的EPEC菌株的基因组草图，以识别与致死性相关的基因簇(潜在的蛋白质编码序列共享≥90%的核苷酸序列同源性)。在确认的14,412个基因簇中，392个基因的存在或不存在与临床结果相关。正如预期的那样，与LI和AI相比，与LI和NSI相关的基因簇更多。来自LI的菌株比来自NSI和AI的菌株更常见的基因簇包括那些编码O抗原生物发生的蛋白质，而编码3型分泌效应因子espJ和OSPB的基因簇在非致死性感染的菌株中更常见。一个编码NleG泛素连接酶变体的基因簇与LI和AI相关，而另外两个nleG簇具有相反的关联。在另外一个更大的NSI和AI GEMS菌株样本中，发现了两个nleG基因簇的类似关联。特定的基因与致命性tEPEC感染有关。对这些因素的进一步研究有可能揭开严重疾病背后的机制，并防止不良后果。在患有中到重度腹泻的婴儿中，典型的肠源性大肠杆菌(TEPEC)菌株与高死亡率有关，但大多数感染tEPEC菌株的婴儿存活下来，有些没有症状。为了研究与严重预后相关的细菌因素，我们测定了70株EPEC菌株的基因组序列。24株tEPEC菌株来自致命感染的儿童。将每个基因的流行率与23名有非致命性症状感染的匹配婴儿和23名有无症状感染的匹配婴儿的菌株进行了比较。我们确定了392个与结果相关的基因，其中一些在致命性感染的菌株中更普遍，而其他基因则不太普遍。这些基因包括几个编码潜在毒力因子的基因，如3型分泌效应器和参与O抗原合成的酶。一项聚合酶链式反应分析证实了编码NleG泛素连接酶变异的等位基因组与临床结果的相关性。对与严重后果相关的因素的进一步研究可能导致新的诊断、治疗和预防策略。
Typical enteropathogenic Escherichia coli (tEPEC) strains were associated with mortality in the Global Enteric Multicenter Study (GEMS). Genetic differences in tEPEC strains could underlie some of the variability in clinical outcome. We produced draft genome sequences of all available tEPEC strains from GEMS lethal infections (LIs) and of closely matched EPEC strains from GEMS subjects with non-lethal symptomatic infections (NSIs) and asymptomatic infections (AIs) to identify gene clusters (potential protein encoding sequences sharing ≥90% nucleotide sequence identity) associated with lethality. Among 14,412 gene clusters identified, the presence or absence of 392 was associated with clinical outcome. As expected, more gene clusters were associated with LI versus AI than LI versus NSI. The gene clusters more prevalent in strains from LI than those from NSI and AI included those encoding proteins involved in O-antigen biogenesis, while clusters encoding type 3 secretion effectors EspJ and OspB were among those more prevalent in strains from non-lethal infections. One gene cluster encoding a variant of an NleG ubiquitin ligase was associated with LI versus AI, while two other nleG clusters had the opposite association. Similar associations were found for two nleG gene clusters in an additional, larger sample of NSI and AI GEMS strains. Particular genes are associated with lethal tEPEC infections. Further study of these factors holds potential to unravel the mechanisms underlying severe disease and to prevent adverse outcomes. Typical enteropathogenic E. coli (tEPEC) strains are associated with high mortality among infants with moderate-to-severe diarrhea, but most infants infected with tEPEC strains survive, and some have no symptoms. To investigate the bacterial factors associated with severe outcome, we determined the genomic sequences of 70 EPEC strains. Twenty four tEPEC strains came from children with lethal infections. The prevalence of each gene was compared to that in strains from 23 matched infants who had non-lethal symptomatic infection and to that in 23 matched infants who had asymptomatic infection. We identified 392 genes associated with outcome, some of which were more prevalent in strains from lethal infections, while others were less prevalent. The genes included several encoding potential virulence factors such as type 3 secreted effectors and enzymes involved in O-antigen synthesis. A PCR assay validated the association of groups of alleles encoding variants of the NleG ubiquitin ligase with clinical outcome. Further study of the factors associated with severe outcome could lead to novel diagnostic, therapeutic and prevention strategies.
登录
查看更多内容
病原体的进化：比较基因组学分析确定了不动杆菌发病机制的遗传途径。
影响因子：
3.7
作者：
Sahl JW;Gillece JD;Schupp JM;Waddell VG;Driebe EM;Engelthaler DM;Keim P
通讯作者：
Keim P
影响因子：
168.9
作者：
Kotloff, Karen L.;Nataro, James P.;Levine, Myron M.
通讯作者：
Levine, Myron M.
影响因子：
5.2
作者：
GILES, C;SANGSTER, G;SMITH, J
通讯作者：
SMITH, J
影响因子：
--
作者：
GILES, C;SANGSTER, G
通讯作者：
SANGSTER, G
DOI：
10.1073/pnas.1306836110
发表时间：
2013-07-30
影响因子：
11.1
作者：
Hazen, Tracy H.;Sahl, Jason W.;Rasko, David A.
通讯作者：
Rasko, David A.