细菌单细胞测序技术研究进展

Advances in bacterial single-cell sequencing

摘要:

细菌群体中细胞间的异质性是决定细菌耐药性和毒力上的关键因素，并在宿主与病原体间的相互作用中起着至关重要的作用，为细菌性感染病的防治带来了重大挑战。单细胞测序是检测细胞异质性的有力工具，但由于细菌独特的生物学特性，如基因组较小、mRNA含量低、半衰期短、无PolyA尾、转录组中rRNA占比高和细胞壁厚等，使得基于真核细胞的单细胞测序方法不能应用于细菌。为了克服这些障碍并促进单细胞技术在细菌研究领域的发展，研究人员成功研发了适用于细菌的单细胞测序方法。本文系统综述了近年来提出的细菌单细胞转录组测序和基因组测序技术，描述了其特点并着重分析了这些技术在揭示细菌耐药性方面的应用，旨在为相关研究提供新的视角。细菌单细胞测序可以深入揭示细菌异质性，提高疾病诊断和治疗的准确性，为细菌学和感染病学的研究提供支持。

Abstract:

Intercellular heterogeneity in bacterial populations is a crucial factor determining bacterial antibiotic resistance and virulence and plays a key role in host-pathogen interactions, posing a major challenge to the control of bacterial infections. Single-cell sequencing is a powerful tool for detecting cellular heterogeneity. However, bacteria have unique biological characteristics such as small genomes, low cellular mRNA contents, and high proportion of rRNAs in the transcriptome, short half-life, polyA tail-lacking mRNA transcripts, and thick cell walls, making the eukaryote-based single-cell sequencing methods impossible to be applied in bacteria. To overcome these obstacles and promote the development of single-cell technology in bacterial research, researchers have successfully developed the single-cell sequencing methods applicable to bacteria. This review systematically summarizes the bacterial single-cell transcriptome sequencing and genome sequencing technologies proposed in recent years, describes their characteristics, and discusses the application prospects of bacterial single-cell sequencing in revealing bacterial drug resistance, aiming to shed light on the subsequent the related research. Bacterial single-cell can deeply reveal bacterial heterogeneity, improve the accuracy of disease diagnosis and treatment, and support microbiological and infectious disease research.