Hurtado-Páez Uriel, Álvarez Zuluaga Nataly, Arango Isaza Rafael Eduardo, Contreras-Moreira Bruno, Rouzaud François, Robledo Jaime
Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia.
Facultad de Ciencias, Universidad Nacional de Colombia (UNAL), Medellín, Colombia.
Front Microbiol. 2023 Jan 4;13:1076797. doi: 10.3389/fmicb.2022.1076797. eCollection 2022.
() lineage 4 is responsible for the highest burden of tuberculosis (TB) worldwide. This lineage has been the most prevalent lineage in Colombia, especially in the North-Eastern (NE) area of Medellin, where it has been shown to have a high prevalence of LAM9 SIT42 and Haarlem1 SIT62 sublineages. There is evidence that regardless of environmental factors and host genetics, differences among sublineages of strains play an important role in the course of infection and disease. Nevertheless, the genetic basis of the success of a sublineage in a specific geographic area remains uncertain. We used a pan-genome-wide association study (pan-GWAS) of 47 strains isolated from NE Medellin between 2005 and 2008 to identify the genes responsible for the phenotypic differences among high and low prevalence sublineages. Our results allowed the identification of 12 variants in 11 genes, of which 4 genes showed the strongest association to low prevalence (, , , and ). The first three have been described as necessary for invasion and intracellular survival. Polymorphisms identified in low prevalence isolates may suggest related to a fitness cost of , which might reflect a decrease in their capacity to be transmitted or to cause an active infection. These results contribute to understanding the success of some sublineages of lineage-4 in a specific geographical area.
4型谱系是全球结核病负担最高的原因。该谱系一直是哥伦比亚最普遍的谱系，特别是在麦德林的东北部地区，在那里已显示LAM9 SIT42和哈勒姆1型SIT62亚谱系具有很高的流行率。有证据表明，无论环境因素和宿主遗传学如何，菌株亚谱系之间的差异在感染和疾病过程中都起着重要作用。然而，特定地理区域中亚谱系成功的遗传基础仍然不确定。我们对2005年至2008年间从麦德林东北部分离出的47株菌株进行了全基因组关联研究（泛基因组全关联研究），以确定导致高流行率和低流行率亚谱系之间表型差异的基因。我们的结果确定了11个基因中的12个变体，其中4个基因与低流行率表现出最强的关联（、、和）。前三个基因已被描述为侵袭和细胞内存活所必需的。在低流行率分离株中鉴定出的多态性可能表明与的适应性代价有关，这可能反映出它们传播或引起活动性感染能力的下降。这些结果有助于理解4型谱系的一些亚谱系在特定地理区域的成功原因。
