Department of Epidemiology of Microbial Disease, Yale School of Public Health, 60 College Street, New Haven, CT, USA.
Department of Mathematics, Simon Fraser University, 8888 University Drive West, Burnaby, BC, Canada.
Nat Commun. 2024 Apr 5;15(1):2962. doi: 10.1038/s41467-024-47282-9.
The projected trajectory of multidrug resistant tuberculosis (MDR-TB) epidemics depends on the reproductive fitness of circulating strains of MDR M. tuberculosis (Mtb). Previous efforts to characterize the fitness of MDR Mtb have found that Mtb strains of the Beijing sublineage (Lineage 2.2.1) may be more prone to develop resistance and retain fitness in the presence of resistance-conferring mutations than other lineages. Using Mtb genome sequences from all culture-positive cases collected over two years in Moldova, we estimate the fitness of Ural (Lineage 4.2) and Beijing strains, the two lineages in which MDR is concentrated in the country. We estimate that the fitness of MDR Ural strains substantially exceeds that of other susceptible and MDR strains, and we identify several mutations specific to these MDR Ural strains. Our findings suggest that MDR Ural Mtb has been transmitting efficiently in Moldova and poses a substantial risk of spreading further in the region.
耐多药结核病(MDR-TB)流行的预测轨迹取决于循环耐多药结核分枝杆菌(MDR Mtb)菌株的生殖适应性。先前对 MDR Mtb 适应性的研究发现,与其他谱系相比,来自北京亚谱系(谱系 2.2.1)的 Mtb 菌株可能更容易在出现耐药相关突变时产生耐药性并保持适应性。我们使用在摩尔多瓦两年内所有培养阳性病例中收集的 Mtb 基因组序列,来估计该国集中存在耐多药的两种谱系(Ural 谱系 4.2 和北京谱系)的 MDR Ural 和北京菌株的适应性。我们估计,MDR Ural 菌株的适应性大大超过了其他敏感和 MDR 菌株,并且我们确定了这些 MDR Ural 菌株特有的几种突变。我们的研究结果表明,MDR Ural Mtb 在摩尔多瓦高效传播,对该地区进一步传播构成了重大威胁。