David Susana, Mateus A R A, Duarte Elsa L, Albuquerque José, Portugal Clara, Sancho Luísa, Lavinha João, Gonçalves Guilherme
Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), Lisboa, Portugal.
Instituto Gulbenkian de Ciência (IGC), Oeiras, Portugal; Institute of Biology, Leiden University, Leiden, The Netherlands.
PLoS One. 2015 Nov 3;10(11):e0140625. doi: 10.1371/journal.pone.0140625. eCollection 2015.
Major contributions from pathogen genome analysis and host genetics have equated the possibility of Mycobacterium tuberculosis co-evolution with its human host leading to more stable sympatric host-pathogen relationships. However, the attribution to either sympatric or allopatric categories depends on the resolution or grain of genotypic characterization. We explored the influence on the sympatric host-pathogen relationship of clinical (HIV infection and multidrug-resistant tuberculosis [MDRTB]) and demographic (gender and age) factors in regards to the genotypic grain by using spacer oligonucleotide typing (spoligotyping) for classification of M. tuberculosis strains within the Euro-American lineage. We analyzed a total of 547 tuberculosis (TB) cases, from six year consecutive sampling in a setting with high TB-HIV coinfection (32.0%). Of these, 62.0% were caused by major circulating pathogen genotypes. The sympatric relationship was defined according to spoligotype in comparison to the international spoligotype database SpolDB4. While no significant association with Euro-American lineage was observed with any of the factors analyzed, increasing the resolution with spoligotyping evidenced a significant association of MDRTB with sympatric strains, regardless of the HIV status. Furthermore, distribution curves of the prevalence of sympatric and allopatric TB in relation to patients' age showed an accentuation of the relevance of the age of onset in the allopatric relationship, as reflected in the trimodal distribution. On the contrary, sympatric TB was characterized by the tendency towards a typical (standard) distribution curve. Our results suggest that within the Euro-American lineage a greater degree of genotyping fine-tuning is necessary in modeling the biological processes behind the host-pathogen interplay. Furthermore, prevalence distribution of sympatric TB to age was suggestive of host genetic determinisms driven by more common variants.
病原体基因组分析和宿主遗传学的重大贡献，使结核分枝杆菌与其人类宿主共同进化并形成更稳定的同域宿主-病原体关系成为可能。然而，同域或异域分类的归属取决于基因分型特征的分辨率或粒度。我们通过使用间隔寡核苷酸分型（spoligotyping）对欧美谱系内的结核分枝杆菌菌株进行分类，探讨了临床（HIV感染和耐多药结核病[MDRTB]）和人口统计学（性别和年龄）因素对同域宿主-病原体关系的影响，这些因素与基因分型粒度有关。我们分析了来自一个结核病-艾滋病病毒合并感染率高（32.0%）的地区连续六年采样的总共547例结核病（TB）病例。其中，62.0%是由主要流行的病原体基因型引起的。与国际spoligotype数据库SpolDB4相比，同域关系是根据spoligotype定义的。虽然在所分析的任何因素中均未观察到与欧美谱系有显著关联，但提高spoligotyping的分辨率表明，无论HIV感染状况如何，MDRTB与同域菌株均存在显著关联。此外，同域和异域结核患病率相对于患者年龄的分布曲线显示，发病年龄在异域关系中的相关性更为突出，这反映在三峰分布中。相反，同域结核的特征是倾向于典型（标准）分布曲线。我们的结果表明，在欧美谱系内，在对宿主-病原体相互作用背后的生物学过程进行建模时，需要更高程度的基因分型微调。此外，同域结核患病率随年龄的分布表明，宿主遗传决定因素是由更常见的变异驱动的。
