a Grupo de Inmunología Celular e Inmunogenética (GICIG), Facultad de Medicina, Universidad de Antioquia , Medellín , Colombia.
b Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia , Medellín , Colombia.
Virulence. 2019 Dec;10(1):695-710. doi: 10.1080/21505594.2019.1642045.
The heterogeneity of the clinical outcome of (Mtb) infection may be due in part to different strategies used by circulating strains to cause disease. This heterogeneity is one of the main limitations to eradicate tuberculosis disease. In this study, we have compared the transcriptional response of two closely related Colombian clinical isolates (UT127 and UT205) of the LAM family under two axenic media conditions. These clinical isolates are phenotypically different at the level of cell death, cytokine production, growth kinetics upon in vitro infection of human tissue macrophages, and membrane vesicle secretion upon culture in synthetic medium. Using RNA-seq, we have identified different pathways that account for two different strategies to cope with the stressful condition of a carbon-poor media such as Sauton's. We showed that the clinical isolate UT205 focus mainly in the activation of virulence systems such as the ESX-1, synthesis of diacyl-trehalose, polyacyl-trehalose, and sulfolipids, while UT127 concentrates its efforts mainly in the survival mode by the activation of the DNA replication, cell division, and lipid biosynthesis. This is an example of two Mtb isolates that belong to the same family and lineage, and even though they have a very similar genome, its transcriptional regulation showed important differences. This results in summary highlight the necessity to reach a better understanding of the heterogeneity in the behavior of these circulating Mtb strains which may help us to design better treatments and vaccines and to identify new targets for drugs.
（Mtb）感染的临床结果的异质性可能部分归因于循环菌株用于引起疾病的不同策略。这种异质性是根除结核病的主要限制之一。在这项研究中，我们比较了两种密切相关的哥伦比亚临床分离株（UT127 和 UT205）在两种体外培养条件下的 LAM 家族的转录反应。这些临床分离株在细胞死亡、细胞因子产生、体外感染人组织巨噬细胞时的生长动力学以及在合成培养基中培养时的膜囊泡分泌水平上表现出不同的表型。使用 RNA-seq，我们确定了不同的途径，这些途径解释了两种不同的策略，以应对类似于 Sauton 培养基这样的贫碳环境的应激条件。我们表明，临床分离株 UT205 主要集中在激活毒力系统，如 ESX-1、二酰基海藻糖、聚酰基海藻糖和硫脂的合成，而 UT127 则主要通过激活 DNA 复制、细胞分裂和脂质生物合成来集中精力维持生存模式。这是两个属于同一家族和谱系的 Mtb 分离株的例子，尽管它们的基因组非常相似，但它们的转录调控显示出重要的差异。这些结果突出强调了有必要更好地了解这些循环 Mtb 菌株行为的异质性，这可能有助于我们设计更好的治疗方法和疫苗，并确定新的药物靶点。
