Duke University School of Medicine, Molecular Genetics and Microbiology, 272 Jones Bldg DUMC 3580, Durham, NC 27710, United States.
Duke University School of Medicine, Molecular Genetics and Microbiology, 272 Jones Bldg DUMC 3580, Durham, NC 27710, United States.
Curr Opin Microbiol. 2020 Apr;54:59-66. doi: 10.1016/j.mib.2020.01.007. Epub 2020 Feb 7.
When Stanley Falkow introduced Molecular Koch's Postulates (Falkow, 1988) as a conceptual framework to identify microbial factors that contributed to disease, he reaffirmed the prominent role that the basic principles of genetic analysis should play in defining genotype-phenotype associations in microbial pathogens. In classical bacterial genetics the nature of mutations is inferred through cis-trans complementation and by indirectly mapping their relative position and physical distance through recombination frequencies - all of which were made possible by the genetic tools of the day: natural transformations, conjugation and transduction. Unfortunately, many of these genetic tools are not always available to study pathogenic bacteria. The recombinant DNA revolution in the 1980s launched the field of molecular pathogenesis as genes could be treated as physical units that could be cut, spliced and transplanted from one microbe to another and thus not only 'prove' that an individual gene complemented a virulence defect in a mutant strain but also could impart pathogenic properties to otherwise benign microbes. The recombinant DNA revolution also enabled the generation of newer versions of genetic tools to generate mutations and engineer microbial genomes. The last decade has ushered in next generation sequencing technologies as a new powerful tool for bacterial genetics. The routine and inexpensive sequencing of microbial genomes has increased the number and phylogenetic scope of microbes that are amenable to functional characterization and experimentation. In this review, we highlight some salient advances in this rapidly evolving area.
当斯坦利·福尔科（Stanley Falkow）引入分子科赫假设（Falkow，1988）作为识别导致疾病的微生物因素的概念框架时，他重申了遗传分析的基本原则在定义微生物病原体的基因型-表型关联方面应发挥的重要作用。在经典细菌遗传学中，突变的性质是通过顺式-反式互补以及通过重组频率间接映射它们的相对位置和物理距离来推断的-所有这些都是由当时的遗传工具实现的：自然转化，共轭和转导。不幸的是，并非总是可以使用这些遗传工具来研究致病菌。20 世纪 80 年代的重组 DNA 革命开创了分子发病机制学领域，因为基因可以被视为可以被切割，拼接和从一种微生物移植到另一种微生物的物理单位，因此不仅可以“证明”单个基因可以弥补突变菌株中的毒力缺陷，而且可以将致病特性赋予原本良性的微生物。重组 DNA 革命还使新一代遗传工具的产生和微生物基因组工程成为可能。过去十年迎来了下一代测序技术，成为细菌遗传学的新强大工具。微生物基因组的常规和廉价测序增加了可进行功能表征和实验的微生物的数量和系统发育范围。在这篇综述中，我们强调了这个快速发展领域的一些显著进展。
