Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs.
Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs.
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DOI：
10.3389/fmicb.2013.00145
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发表时间：
2013
影响因子：
5.2
通讯作者：
Dantas G
中科院分区：
文献类型：
--
作者：
Pehrsson EC;Forsberg KJ;Gibson MK;Ahmadi S;Dantas G
在过去的几十年里，耐药性细菌的感染率急剧增加，带来了深远的医疗保健和社会成本。最近的证据已经建立了人类病原体中的抗生素耐药性基因与非致病性，真菌和环境生物中发现的抗生素耐药性基因之间的联系，促使对天然和人类相关的抗生素耐药性水库进行更深入的研究。功能性宏基因组选择，其中选择鸟枪克隆的DNA片段赋予指示宿主存活的能力，已越来越多地应用于许多抗生素耐药性储库的表征。这些实验已经证明抗生素抗性基因是高度多样的并且广泛分布，许多时候与已知序列几乎没有相似性。通过对抗生素暴露的生存进行无偏选择，功能宏基因组学可以通过减少假阳性耐药的发现和允许识别以前无法识别的耐药基因来改善注释。在这篇综述中，我们总结了新的电阻功能发现使用功能宏基因组研究自然和人类影响的电阻水库。新的抗生素抗性基因的例子包括那些与已知序列高度不同的基因、那些序列完全不能预测抗性功能的基因、双功能抗性基因和那些具有非常规、非典型抗性机制的基因。在临床上克服抗生素耐药性将需要更好地了解现有的耐药性储存库和控制水平基因交换的传播网络，为限制耐药性基因向人类病原体传播的最佳实践提供信息。
Rates of infection with antibiotic-resistant bacteria have increased precipitously over the past several decades, with far-reaching healthcare and societal costs. Recent evidence has established a link between antibiotic resistance genes in human pathogens and those found in non-pathogenic, commensal, and environmental organisms, prompting deeper investigation of natural and human-associated reservoirs of antibiotic resistance. Functional metagenomic selections, in which shotgun-cloned DNA fragments are selected for their ability to confer survival to an indicator host, have been increasingly applied to the characterization of many antibiotic resistance reservoirs. These experiments have demonstrated that antibiotic resistance genes are highly diverse and widely distributed, many times bearing little to no similarity to known sequences. Through unbiased selections for survival to antibiotic exposure, functional metagenomics can improve annotations by reducing the discovery of false-positive resistance and by allowing for the identification of previously unrecognizable resistance genes. In this review, we summarize the novel resistance functions uncovered using functional metagenomic investigations of natural and human-impacted resistance reservoirs. Examples of novel antibiotic resistance genes include those highly divergent from known sequences, those for which sequence is entirely unable to predict resistance function, bifunctional resistance genes, and those with unconventional, atypical resistance mechanisms. Overcoming antibiotic resistance in the clinic will require a better understanding of existing resistance reservoirs and the dissemination networks that govern horizontal gene exchange, informing best practices to limit the spread of resistance-conferring genes to human pathogens.
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影响因子：
5.4
作者：
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通讯作者：
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DOI：
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