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功能宏基因组学揭示的新型土壤来源β-内酰胺、氯霉素、磷霉素和甲氧苄啶抗性基因

Novel Soil-Derived Beta-Lactam, Chloramphenicol, Fosfomycin and Trimethoprim Resistance Genes Revealed by Functional Metagenomics.

作者信息

Willms Inka Marie, Grote Maja, Kocatürk Melissa, Singhoff Lukas, Kraft Alina Andrea, Bolz Simon Henning, Nacke Heiko

机构信息

Department of Genomic and Applied Microbiology and Göttingen Genomics Laboratory, Institute of Microbiology and Genetics, Georg-August University of Göttingen, D-37077 Göttingen, Germany.

出版信息

Antibiotics (Basel). 2021 Apr 3;10(4):378. doi: 10.3390/antibiotics10040378.

DOI:10.3390/antibiotics10040378
PMID:33916668
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8066302/
Abstract

Antibiotic resistance genes (ARGs) in soil are considered to represent one of the largest environmental resistomes on our planet. As these genes can potentially be disseminated among microorganisms via horizontal gene transfer (HGT) and in some cases are acquired by clinical pathogens, knowledge about their diversity, mobility and encoded resistance spectra gained increasing public attention. This knowledge offers opportunities with respect to improved risk prediction and development of strategies to tackle antibiotic resistance, and might help to direct the design of novel antibiotics, before further resistances reach hospital settings or the animal sector. Here, metagenomic libraries, which comprise genes of cultivated microorganisms, but, importantly, also those carried by the uncultured microbial majority, were screened for novel ARGs from forest and grassland soils. We detected three new beta-lactam, a so far unknown chloramphenicol, a novel fosfomycin, as well as three previously undiscovered trimethoprim resistance genes. These ARGs were derived from phylogenetically diverse soil bacteria and predicted to encode antibiotic inactivation, antibiotic efflux, or alternative variants of target enzymes. Moreover, deduced gene products show a minimum identity of ~21% to reference database entries and confer high-level resistance. This highlights the vast potential of functional metagenomics for the discovery of novel ARGs from soil ecosystems.

摘要

土壤中的抗生素抗性基因(ARGs)被认为是地球上最大的环境抗性组之一。由于这些基因可能通过水平基因转移(HGT)在微生物之间传播,并且在某些情况下会被临床病原体获得,因此关于它们的多样性、流动性和编码的抗性谱的知识越来越受到公众关注。这些知识为改进风险预测和制定应对抗生素抗性的策略提供了机会,并且在进一步的抗性传播到医院环境或动物领域之前,可能有助于指导新型抗生素的设计。在这里,我们从森林和草原土壤的宏基因组文库中筛选新型ARGs,这些文库不仅包含已培养微生物的基因,重要的是还包含未培养的大多数微生物携带的基因。我们检测到了三种新的β-内酰胺类、一种迄今未知的氯霉素、一种新型磷霉素以及三种以前未发现的甲氧苄啶抗性基因。这些ARGs来源于系统发育上不同的土壤细菌,预计编码抗生素失活、抗生素外排或靶标酶的替代变体。此外,推导的基因产物与参考数据库条目显示出至少约21%的一致性,并赋予高水平抗性。这突出了功能宏基因组学在从土壤生态系统中发现新型ARGs方面的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a6e/8066302/e26ca673f5b9/antibiotics-10-00378-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a6e/8066302/7801c10689f2/antibiotics-10-00378-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a6e/8066302/93ba266ca188/antibiotics-10-00378-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a6e/8066302/dc9f2fd18800/antibiotics-10-00378-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a6e/8066302/e26ca673f5b9/antibiotics-10-00378-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a6e/8066302/7801c10689f2/antibiotics-10-00378-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a6e/8066302/93ba266ca188/antibiotics-10-00378-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a6e/8066302/dc9f2fd18800/antibiotics-10-00378-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a6e/8066302/e26ca673f5b9/antibiotics-10-00378-g004.jpg

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本文引用的文献

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β-lactam antibiotics: An overview from a medicinal chemistry perspective.β-内酰胺类抗生素:从药物化学角度综述。
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Potential of fosfomycin in treating multidrug-resistant infections in children.磷霉素治疗儿童多重耐药感染的潜力。
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Functional and Structural Roles of the Major Facilitator Superfamily Bacterial Multidrug Efflux Pumps.
农业活动影响下连通地表水系统中的抗生素耐药基因。
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