Dissemination of cephalosporin resistance genes between Escherichia coli strains from farm animals and humans by specific plasmid lineages.
Dissemination of cephalosporin resistance genes between Escherichia coli strains from farm animals and humans by specific plasmid lineages.
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DOI：
10.1371/journal.pgen.1004776
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发表时间：
2014-12
期刊：
影响因子：
4.5
通讯作者：
van Schaik W
中科院分区：
文献类型：
--
作者：
de Been M;Lanza VF;de Toro M;Scharringa J;Dohmen W;Du Y;Hu J;Lei Y;Li N;Tooming-Klunderud A;Heederik DJ;Fluit AC;Bonten MJ;Willems RJ;de la Cruz F;van Schaik W
第三代头孢菌素是一类β-内酰胺类抗生素，常用于治疗由革兰氏阴性菌引起的人类感染，特别是大肠杆菌。令人担忧的是，由第三代头孢菌素耐药大肠杆菌引起的人类感染的发病率在全球范围内正在上升。最近的研究表明，这些大肠杆菌菌株及其抗生素耐药性基因可以通过食物链从食品类动物传播到人类。然而，这些研究使用了传统的分型方法，这可能没有提供足够的分辨率来可靠地评估这些菌株的相关性。因此，我们使用全基因组测序(WGS)来研究人、鸡肉、家禽和猪的头孢菌素耐药大肠杆菌的相关性。其中一个菌株收集包括成对的人和家禽相关菌株，这些菌株以前被认为是基于多位点序列分型、质粒分型和抗生素耐药性基因测序而相同的。第二个收集包括来自农民和他们的猪的分离物。WGS分析显示，人和家禽相关分离株之间存在相当大的异质性。来自两个来源的最接近的菌株对每MBP核心基因组携带1263个单核苷酸多态(SNPs)。相比之下，来自人和猪的流行病学相关菌株每MBP核心基因组仅有1.8个SNPs。基于WGS的重组质粒显示，三种不同的质粒族(IncI1和IncK型)携带了超广谱β-内酰胺酶(ESBL)和AmpC酶(AmpC)型头孢菌素耐药基因。每个谱系中的质粒骨实际上是相同的，并且由遗传上不相关的人和动物分离株共享。通过对两株菌株的长读DNA测序验证了由短读测序数据构建的质粒的有效性。我们的发现未能证明，根据传统的低分辨率分型方法，最近头孢菌素耐药大肠杆菌菌株从家禽到人类的克隆性传播的证据。相反，我们的数据表明，头孢菌素耐药基因主要通过不同的质粒在动物和人类中传播。对包括第三代头孢菌素在内的临床相关抗菌药产生抗药性的大肠杆菌感染在全球迅速上升，这是令人担忧的原因。家畜，特别是家禽的肠道是耐药大肠杆菌的重要储存库，但目前尚不清楚这些细菌能在多大程度上传播给人类。食物被认为是一个重要的来源，因为在供食用的动物和肉制品中已经检测到耐药大肠杆菌。之前使用传统的低分辨率基因分型方法的研究发现，人和家禽中存在的耐药大肠杆菌彼此无法区分，这表明这些细菌通过食物链传播给人类。然而，通过应用高分辨率的全基因组测序方法，我们没有发现细菌通过食物链进行这种传播的证据。相反，通过使用一种新的方法从全基因组序列数据中重建可移动的遗传元件，我们发现来自人类和动物来源的遗传无关的大肠杆菌分离株携带几乎相同的质粒，编码第三代头孢菌素耐药决定因素。我们的数据表明，头孢菌素耐药性主要是通过在动物和人类之间转移可移动的遗传元件来传播的。
Third-generation cephalosporins are a class of β-lactam antibiotics that are often used for the treatment of human infections caused by Gram-negative bacteria, especially Escherichia coli. Worryingly, the incidence of human infections caused by third-generation cephalosporin-resistant E. coli is increasing worldwide. Recent studies have suggested that these E. coli strains, and their antibiotic resistance genes, can spread from food-producing animals, via the food-chain, to humans. However, these studies used traditional typing methods, which may not have provided sufficient resolution to reliably assess the relatedness of these strains. We therefore used whole-genome sequencing (WGS) to study the relatedness of cephalosporin-resistant E. coli from humans, chicken meat, poultry and pigs. One strain collection included pairs of human and poultry-associated strains that had previously been considered to be identical based on Multi-Locus Sequence Typing, plasmid typing and antibiotic resistance gene sequencing. The second collection included isolates from farmers and their pigs. WGS analysis revealed considerable heterogeneity between human and poultry-associated isolates. The most closely related pairs of strains from both sources carried 1263 Single-Nucleotide Polymorphisms (SNPs) per Mbp core genome. In contrast, epidemiologically linked strains from humans and pigs differed by only 1.8 SNPs per Mbp core genome. WGS-based plasmid reconstructions revealed three distinct plasmid lineages (IncI1- and IncK-type) that carried cephalosporin resistance genes of the Extended-Spectrum Beta-Lactamase (ESBL)- and AmpC-types. The plasmid backbones within each lineage were virtually identical and were shared by genetically unrelated human and animal isolates. Plasmid reconstructions from short-read sequencing data were validated by long-read DNA sequencing for two strains. Our findings failed to demonstrate evidence for recent clonal transmission of cephalosporin-resistant E. coli strains from poultry to humans, as has been suggested based on traditional, low-resolution typing methods. Instead, our data suggest that cephalosporin resistance genes are mainly disseminated in animals and humans via distinct plasmids. The rapid global rise of infections caused by Escherichia coli that are resistant to clinically relevant antimicrobials, including third-generation cephalosporins, is cause for concern. The intestinal tract of livestock, in particular poultry, is an important reservoir for drug resistant E. coli, but it is unknown to what extent these bacteria can spread to humans. Food is thought to be an important source because drug-resistant E. coli have been detected in animals raised for meat consumption and in meat products. Previous studies that used traditional, low-resolution, genetic typing methods found that drug resistant E. coli present in humans and poultry were indistinguishable from each other, suggesting dissemination of these bacteria through the food-chain to humans. However, by applying high-resolution, whole-genome sequencing methods, we did not find evidence for such transmission of bacteria through the food-chain. Instead, by employing a novel approach for the reconstruction of mobile genetic elements from whole-genome sequence data, we discovered that genetically unrelated E. coli isolates from both humans and animal sources carried nearly identical plasmids that encode third-generation cephalosporin resistance determinants. Our data suggest that cephalosporin resistance is mainly disseminated via the transfer of mobile genetic elements between animals and humans.
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核心基因组中最近的重组事件与粪肠球菌的自适应进化有关。
影响因子：
3.3
作者：
de Been M;van Schaik W;Cheng L;Corander J;Willems RJ
通讯作者：
Willems RJ
影响因子：
5.2
作者：
Garcia-Fernandez, Aurora;Chiaretto, Giuseppina;Carattoli, Alessandra
通讯作者：
Carattoli, Alessandra
影响因子：
11.8
作者：
de Sande-Bruinsma, Nienke Van;Grundmann, Hajo;Verloo, Didier;Tiemersma, Edine;Monen, Jos;Goossens, Herman;Ferech, Matus
通讯作者：
Ferech, Matus
DOI：
10.1093/bioinformatics/btp348
发表时间：
2009-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Capella-Gutiérrez S;Silla-Martínez JM;Gabaldón T
通讯作者：
Gabaldón T
DOI：
10.1016/j.diagmicrobio.2009.08.011
发表时间：
2009-12-01
影响因子：
2.9
作者：
Baudry, Patricia J.;Mataseje, Laura;Mulvey, Michael R.
通讯作者：
Mulvey, Michael R.