Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis.
Rapid adaptation of a complex trait during experimental evolution of Mycobacterium tuberculosis.
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DOI：
10.7554/elife.78454
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发表时间：
2022-06-21
期刊：
影响因子：
7.7
通讯作者：
Pepperell, Caitlin S.
中科院分区：
文献类型：
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作者：
Smith, Tracy M.;Youngblom, Madison A.;Kernien, John F.;Mohamed, Mohamed A.;Fry, Sydney S.;Bohr, Lindsey L.;Mortimer, Tatum D.;O'Neill, Mary B.;Pepperell, Caitlin S.
由结核分枝杆菌（M. TB）引起的结核病是传染病导致死亡的主要原因。结核病传统上与生物膜无关，但结核分枝杆菌生物膜与药物和免疫耐受性有关，人们越来越认识到它们对结核病感染的抵抗力的贡献。在这里，我们使用结核分枝杆菌实验进化来研究这种复杂的表型，并确定控制生物膜形成的候选位点。我们发现了新的候选位点，增加了我们对结核分枝杆菌生物膜发育的遗传结构的理解。在作为生物膜生长的选择压力下，调控突变迅速席卷到固定，并与多种性状的变化相关，包括细胞外基质的产生、细胞大小和生长速度。根据亲本菌株的遗传背景，促进生物膜生长的遗传和表型途径各不相同，这表明上位性相互作用在结核分枝杆菌适应不断变化的环境中很重要。在许多环境中，细菌生活在称为生物膜的结构中。生物膜中的细胞相互协调，保护群体，使其能够在困难的条件下生存。引起结核病的结核分枝杆菌感染人体后会形成生物膜。生物膜使感染更加难以治疗，这可能是结核病是世界上最致命的细菌感染的原因之一。细菌在一次感染过程中进化迅速，但形成生物膜的细菌与单独生活的细菌进化不同。这种进化是通过细菌DNA的突变发生的，这种突变可以是很小的（DNA序列中的单个碱基变为不同的碱基），也可以是较大的变化（例如几个碱基的删除或插入）。Smith， Youngblom等人在实验室中研究了结核在生物膜中生长的进化过程。随着细菌的进化，它们倾向于形成更厚的生物膜，这种效应与14个涉及单碱基DNA变化的突变和4个较大的突变有关。大多数变化发生在DNA的调控区域，该区域控制着基因是否被细胞“读取”以产生蛋白质。这些区域在进化过程中往往比编码蛋白质的区域变化更大，因为它们对一组相关基因有协调作用，而不是随机改变单个基因。Smith， Youngblom等人还表明，由不同结核菌株制成的生物膜以不同的方式进化。Smith Youngblom等人的发现提供了更多关于细菌如何适应生物膜生活的信息，这可能会揭示控制它们的新方法。这可以应用于水处理、食品生产和医疗保健。了解如何治疗在生物膜中生长的细菌也可以改善感染结核病患者的预后。
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is a leading cause of death due to infectious disease. TB is not traditionally associated with biofilms, but M. tb biofilms are linked with drug and immune tolerance and there is increasing recognition of their contribution to the recalcitrance of TB infections. Here, we used M. tb experimental evolution to investigate this complex phenotype and identify candidate loci controlling biofilm formation. We identified novel candidate loci, adding to our understanding of the genetic architecture underlying M. tb biofilm development. Under selective pressure to grow as a biofilm, regulatory mutations rapidly swept to fixation and were associated with changes in multiple traits, including extracellular matrix production, cell size, and growth rate. Genetic and phenotypic paths to enhanced biofilm growth varied according to the genetic background of the parent strain, suggesting that epistatic interactions are important in M. tb adaptation to changing environments. In many environments, bacteria live together in structures called biofilms. Cells in biofilms coordinate with each other to protect the group and allow it to survive difficult conditions. Mycobacterium tuberculosis, the bacterium that causes tuberculosis, forms biofilms when it infects the human body. Biofilms make the infection a lot more difficult to treat, which may be one of the reasons why tuberculosis is the deadliest bacterial infection in the world. Bacteria evolve rapidly over the course of a single infection, but bacteria forming biofilms evolve differently to bacteria living alone. This evolution happens through mutations to the bacterial DNA, which can be small (a single base in a DNA sequence changes to a different base) or larger changes (such as the deletion or insertion of several bases). Smith, Youngblom et al. studied the evolution of tuberculosis growing in biofilms in the lab. As the bacteria evolved, they tended to form thicker biofilms, an effect linked to 14 mutations involving single base DNA changes and four larger ones. Most of the changes were in regulatory regions of DNA, which control whether genes are ‘read’ by cells to produce proteins. These regions often change more though evolution than regions coding for proteins, because they have a coordinated effect on a group of related genes rather than randomly altering individual genes. Smith, Youngblom et al. also showed that biofilms made from different strains of tuberculosis evolved in different ways. Smith Youngblom et al.’s findings provide more information regarding how bacteria adapt to living in biofilms, which may reveal new ways to control them. This could have applications in water treatment, food production and healthcare. Learning how to treat bacteria growing in biofilms could also improve the outcomes for patients infected with tuberculosis.