Center for Genomic Sciences, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, U.S.A.
Center for Advanced Microbial Processing, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, U.S.A.
Biochem Soc Trans. 2020 Dec 18;48(6):2437-2455. doi: 10.1042/BST20190713.
The principle of monoclonality with regard to bacterial infections was considered immutable prior to 30 years ago. This view, espoused by Koch for acute infections, has proven inadequate regarding chronic infections as persistence requires multiple forms of heterogeneity among the bacterial population. This understanding of bacterial plurality emerged from a synthesis of what-were-then novel technologies in molecular biology and imaging science. These technologies demonstrated that bacteria have complex life cycles, polymicrobial ecologies, and evolve in situ via the horizontal exchange of genic characters. Thus, there is an ongoing generation of diversity during infection that results in far more highly complex microbial communities than previously envisioned. This perspective is based on the fundamental tenet that the bacteria within an infecting population display genotypic diversity, including gene possession differences, which result from horizontal gene transfer mechanisms including transformation, conjugation, and transduction. This understanding is embodied in the concepts of the supragenome/pan-genome and the distributed genome hypothesis (DGH). These paradigms have fostered multiple researches in diverse areas of bacterial ecology including host-bacterial interactions covering the gamut of symbiotic relationships including mutualism, commensalism, and parasitism. With regard to the human host, within each of these symbiotic relationships all bacterial species possess attributes that contribute to colonization and persistence; those species/strains that are pathogenic also encode traits for invasion and metastases. Herein we provide an update on our understanding of bacterial plurality and discuss potential applications in diagnostics, therapeutics, and vaccinology based on perspectives provided by the DGH with regard to the evolution of pathogenicity.
30 年前，人们普遍认为细菌性感染遵循单克隆原则，这一观点是由科赫提出的，他认为急性感染是由单一细菌引起的。然而，这一观点对于慢性感染并不适用，因为细菌的持续存在需要细菌群体中存在多种形式的异质性。这一关于细菌多样性的理解源于分子生物学和成像科学等新技术的综合应用。这些技术表明，细菌具有复杂的生命周期、多微生物生态系统，并且通过基因特征的水平交换在原位进化。因此，在感染过程中会不断产生多样性，导致形成的微生物群落比以前想象的要复杂得多。这一观点基于一个基本前提，即在感染人群中的细菌表现出基因型多样性，包括由于水平基因转移机制（包括转化、 conjugation 和 transduction）而导致的基因拥有差异。这一理解体现在超基因组/泛基因组和分布式基因组假说（DGH）的概念中。这些范式促进了细菌生态学各个领域的多项研究，包括涵盖共生关系（包括互利共生、共生和寄生）的宿主-细菌相互作用。就人类宿主而言，在这些共生关系中的每一种关系中，所有细菌物种都具有有助于定殖和持续存在的特性；那些具有致病性的物种/菌株也编码了入侵和转移的特征。本文我们将更新对细菌多样性的理解，并根据 DGH 提供的关于致病性进化的观点，讨论其在诊断、治疗和疫苗学方面的潜在应用。
