Genome-Based Prediction of Bacterial Antibiotic Resistance.
Genome-Based Prediction of Bacterial Antibiotic Resistance.
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DOI：
10.1128/jcm.01405-18
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发表时间：
2019-03
影响因子：
9.4
通讯作者：
Read TD
中科院分区：
文献类型：
--
作者：
Su M;Satola SW;Read TD
长期以来，临床微生物学一直依赖于培养细菌来确定抗生素敏感性，但使用全基因组测序进行抗生素敏感性测试（WGS-AST）现在是一个强大的替代方案。这篇综述讨论了使这成为可能的技术，并介绍了最近的研究结果，以预测基于基因组序列的抗性。长期以来，临床微生物学一直依赖于培养细菌来确定抗生素敏感性，但使用全基因组测序进行抗生素敏感性测试（WGS-AST）现在是一个强大的替代方案。这篇综述讨论了使这成为可能的技术，并介绍了最近的研究结果，以预测基于基因组序列的抗性。我们通过简单地存在或不存在先前已知的基因和单核苷酸多态性（SNP）来研究调用抗生素耐药性谱与部署机器学习和统计模型的方法之间的差异。通常，基于基因组的预测的局限性来自于基于培养的AST的准确性的局限性，以及对抗性遗传基础的不完整了解。然而，即使基于基因组的预测变得越来越普遍，我们也需要保持表型测试，以确保结果不会随着时间的推移而出现分歧。我们认为，WGS-AST的标准化的挑战与一致的表型菌株集定义的遗传多样性是必要的，以比较基于基因组序列的抗生素耐药性预测方法的有效性。
Clinical microbiology has long relied on growing bacteria in culture to determine antimicrobial susceptibility profiles, but the use of whole-genome sequencing for antibiotic susceptibility testing (WGS-AST) is now a powerful alternative. This review discusses the technologies that made this possible and presents results from recent studies to predict resistance based on genome sequences. Clinical microbiology has long relied on growing bacteria in culture to determine antimicrobial susceptibility profiles, but the use of whole-genome sequencing for antibiotic susceptibility testing (WGS-AST) is now a powerful alternative. This review discusses the technologies that made this possible and presents results from recent studies to predict resistance based on genome sequences. We examine differences between calling antibiotic resistance profiles by the simple presence or absence of previously known genes and single-nucleotide polymorphisms (SNPs) against approaches that deploy machine learning and statistical models. Often, the limitations to genome-based prediction arise from limitations of accuracy of culture-based AST in addition to an incomplete knowledge of the genetic basis of resistance. However, we need to maintain phenotypic testing even as genome-based prediction becomes more widespread to ensure that the results do not diverge over time. We argue that standardization of WGS-AST by challenge with consistently phenotyped strain sets of defined genetic diversity is necessary to compare the efficacy of methods of prediction of antibiotic resistance based on genome sequences.