Talarico Sarah, Cave M Donald, Foxman Betsy, Marrs Carl F, Zhang Lixin, Bates Joseph H, Yang Zhenhua
Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory Street, 4648 SPH I, Ann Arbor, MI 48109, USA.
Tuberculosis (Edinb). 2007 Jul;87(4):338-46. doi: 10.1016/j.tube.2007.03.003. Epub 2007 May 1.
There is evidence that some members of the Mycobacterium tuberculosis PE PGRS gene subfamily, including PE PGRS33, may have a specific function in M. tuberculosis persistence. The impact of naturally-occurring PE PGRS33 genetic variations on the virulence and transmissibility of clinical M. tuberculosis isolates is not known. We used PCR and DNA sequencing to identify genetic variations in the PE PGRS33 gene in comparison with the sequenced laboratory strain, H37Rv, among 649 isolates from a population-based sample. The PE PGRS33 alleles were placed into two groups, based on the effect of the sequence variations on the PE PGRS33 protein, and their associations with clinical and epidemiological characteristics were assessed using multivariate logistic regression to control for potential confounding of host-related factors. Of the 639 isolates for which sequence data were obtained, 139 (21.8%) had PE PGRS33 alleles that would result in a significant change to the PE PGRS33 protein due to large insertions/deletions or frameshift mutations. These isolates were significantly associated with clustering based on genotype and absence of cavitations in the lungs, compared to isolates having PE PGRS33 alleles that would result in no or minimal change to the PE PGRS33 protein. The association of significant changes to PE PGRS33 with clinical and epidemiological characteristics suggests that PE PGRS33 may have an important role in M. tuberculosis persistence.
有证据表明，结核分枝杆菌PE PGRS基因亚家族的一些成员，包括PE PGRS33，可能在结核分枝杆菌的潜伏中具有特定功能。目前尚不清楚自然发生的PE PGRS33基因变异对临床结核分枝杆菌分离株的毒力和传播性的影响。我们使用聚合酶链反应（PCR）和DNA测序，与已测序的实验室菌株H37Rv相比，在一个基于人群的样本中的649株分离株中鉴定PE PGRS33基因的遗传变异。根据序列变异对PE PGRS33蛋白的影响，将PE PGRS33等位基因分为两组，并使用多变量逻辑回归评估它们与临床和流行病学特征的关联，以控制宿主相关因素的潜在混杂影响。在获得序列数据的639株分离株中，139株（21.8%）的PE PGRS33等位基因会因大的插入/缺失或移码突变而导致PE PGRS33蛋白发生显著变化。与具有不会导致或只会导致PE PGRS33蛋白最小变化的PE PGRS33等位基因的分离株相比，这些分离株与基于基因型的聚集以及肺部无空洞显著相关。PE PGRS33的显著变化与临床和流行病学特征之间的关联表明，PE PGRS33可能在结核分枝杆菌的潜伏中起重要作用。
