高通量测序技术在细菌耐药中的应用

细菌耐药已成为威胁全球人类公共健康的重要因素之一,快速、准确明确细菌耐药的特性、机制及传播特征对疾病治疗及控制耐药菌的传播具有重要意义。高通量测序技术可以同时平行检测多个基因序列的状态,已广泛应用于细菌耐药检测。目前高通量测序技术在细菌耐药领域的应用主要有:全基因组测序技术、目标区域测序技术和宏基因组测序技术。所采用的测序平台主要为Illumina、Ion Torrent、BGI等二代测序和Pacific Biosciences、Oxford Nonopore 等三代测序平台。通过细菌耐药基因预测细菌耐药表型的准确性在很大程度上依赖于成熟的专业耐药基因数据库,各种通用型、特异型及隐马尔可夫模型耐药基因数据库的建立和完善,为高通量测序技术在细菌耐药领域的应用提供了坚实的基础。本文简要介绍了高通量测序技术、数据分析方法及相应测序平台在细菌耐药领域中的应用进展,并同时介绍了细菌耐药数据库的现状。

High Throughput Sequencing in Antimicrobial Resistance-the State of the Art

Antimicrobial resistance (AMR) is one of the greatest concerns for human health globally. Developing rapid and accurate methods to identify and characterize AMR is critical to improve patient outcome and limit the spread of antibiotic resistance. High throughput sequencing allows for high-throughput massively sequencing of thousands to billions of DNA fragments independently and simultaneously being used to identify AMR. The 3 main applications of high throughput sequencing in AMR include whole genome sequencing (WGS), targeted NGS (tNGS) and metagenomics NGS (mNGS). The sequencing platforms include the second sequencing platforms (Illumina, Ion Torrent, BGIseq) and the third sequencing platforms (Pacific Biosciences, Oxford Nonopore). The computational prediction of AMR depends largely on the maturation of well-curated gene databases of antimicrobial resistance. Generalized, specialized and hidden Markov model-based databases have been developed and updated continuously. We highlighted the high throughput sequencing technologies, computational methods, platforms and AMR databases used in antimicrobial resistance studies.