Computational discovery and functional validation of novel fluoroquinolone resistance genes in public metagenomic data sets.
Computational discovery and functional validation of novel fluoroquinolone resistance genes in public metagenomic data sets.
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DOI：
10.1186/s12864-017-4064-0
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发表时间：
2017-09-02
期刊：
影响因子：
4.4
通讯作者：
Kristiansson E
中科院分区：
文献类型：
--
作者：
Boulund F;Berglund F;Flach CF;Bengtsson-Palme J;Marathe NP;Larsson DGJ;Kristiansson E
氟喹诺酮类是用于预防和治疗各种细菌感染的广谱抗生素。质粒介导的qnr基因在许多细菌物种中提供对氟喹诺酮类药物的耐药性，并且在临床环境中越来越多地遇到。在过去的十年中，几个qnr基因家族被发现并被鉴定，但它们真正的流行和多样性仍然不清楚。特别是，环境和宿主相关的细菌群落已经被假设为维持大量未知的qnr基因集合，这些基因可以被动员到病原体中。在这项研究中，我们使用计算方法来筛选新的qnr基因的基因组和宏基因组。与以前的研究相比，我们分析了一个几乎20倍大的数据集，包括近13个序列数据。总共鉴定了362，843个潜在的qnr基因片段，从中重建了611个推定的qnr基因。这些基因序列包括所有先前描述的质粒介导的qnr基因家族。在611个已识别的qnr基因中，有52个是从宏基因组中重建的，其中20个以前从未描述过。所有新的qnr基因都是由与水生环境相关的宏基因组组装而成的。九个新的基因被选中进行验证，和六个测试的基因赋予一致降低敏感性环丙沙星在大肠杆菌中表达时。本研究的结果为qnr基因在环境微生物群落中的普遍存在提供了额外的证据，扩大了已知qnr基因变体的数量，并进一步阐明了这类抗性基因的多样性。这项研究也加强了这样一个假设，即环境中的细菌群落是以前未被描述的qnr基因的来源。本文的在线版本（doi：10.1186/s12864-017-4064-0）包含补充材料，可供授权用户使用。
Fluoroquinolones are broad-spectrum antibiotics used to prevent and treat a wide range of bacterial infections. Plasmid-mediated qnr genes provide resistance to fluoroquinolones in many bacterial species and are increasingly encountered in clinical settings. Over the last decade, several families of qnr genes have been discovered and characterized, but their true prevalence and diversity still remain unclear. In particular, environmental and host-associated bacterial communities have been hypothesized to maintain a large and unknown collection of qnr genes that could be mobilized into pathogens. In this study we used computational methods to screen genomes and metagenomes for novel qnr genes. In contrast to previous studies, we analyzed an almost 20-fold larger dataset comprising almost 13 terabases of sequence data. In total, 362,843 potential qnr gene fragments were identified, from which 611 putative qnr genes were reconstructed. These gene sequences included all previously described plasmid-mediated qnr gene families. Fifty-two of the 611 identified qnr genes were reconstructed from metagenomes, and 20 of these were previously undescribed. All of the novel qnr genes were assembled from metagenomes associated with aquatic environments. Nine of the novel genes were selected for validation, and six of the tested genes conferred consistently decreased susceptibility to ciprofloxacin when expressed in Escherichia coli. The results presented in this study provide additional evidence for the ubiquitous presence of qnr genes in environmental microbial communities, expand the number of known qnr gene variants and further elucidate the diversity of this class of resistance genes. This study also strengthens the hypothesis that environmental bacterial communities act as sources of previously uncharacterized qnr genes. The online version of this article (doi:10.1186/s12864-017-4064-0) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
4.9
作者：
Cavaco, L. M.;Hasman, H.;Aarestrup, F. M.
通讯作者：
Aarestrup, F. M.
DOI：
10.1186/1476-0711-12-34
发表时间：
2013-11-21
影响因子：
5.7
作者：
Flach, Carl-Fredrik;Boulund, Fredrik;Larsson, D. G. Joakim
通讯作者：
Larsson, D. G. Joakim
影响因子：
4.4
作者：
Boulund, Fredrik;Johnning, Anna;Kristiansson, Erik
通讯作者：
Kristiansson, Erik
影响因子：
14.9
作者：
Cochrane G;Alako B;Amid C;Bower L;Cerdeño-Tárraga A;Cleland I;Gibson R;Goodgame N;Jang M;Kay S;Leinonen R;Lin X;Lopez R;McWilliam H;Oisel A;Pakseresht N;Pallreddy S;Park Y;Plaister S;Radhakrishnan R;Rivière S;Rossello M;Senf A;Silvester N;Smirnov D;Ten Hoopen P;Toribio A;Vaughan D;Zalunin V
通讯作者：
Zalunin V