Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection.
Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection.
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结核分枝杆菌 (Mtb) 已造成全球健康灾难，而耐药 Mtb 菌株的出现更是雪上加霜。我们使用全基因组测序来比较从食蟹猴分离出的结核分枝杆菌中突变的积累与活动性、潜伏性和再活动性疾病。根据观察到的 SNP 分布，我们计算了这些疾病状态的突变率。我们的数据表明，尽管潜伏感染期间细菌复制减少，但结核分枝杆菌在潜伏期间获得的染色体突变数量与活动性疾病期间或同一时间段内对数生长的培养物中发生的染色体突变数量相似。多态性模式表明体内突变负担是由于 DNA 氧化损伤造成的。因此，我们证明 Mtb 在潜伏期间继续获得突变，并为潜伏性结核病的异烟肼单药治疗是出现 INH 耐药性的危险因素这一观察结果提供了新的解释。
Mycobacterium tuberculosis (Mtb) has generated a global health catastrophe that has been compounded by the emergence of drug resistant Mtb strains. We used whole genome sequencing to compare the accumulation of mutations in Mtb isolated from cynomolgus macaques with active, latent and reactivated disease. Based on the distribution of SNPs observed, we calculated the mutation rates for these disease states. Our data suggest that Mtb acquires a similar number of chromosomal mutations during latency as occurs during active disease or in a logarithmically growing culture over the same period of time despite reduced bacterial replication during latent infection. The pattern of polymorphisms suggests that the mutational burden in vivo is due to oxidative DNA damage. Thus, we demonstrate that Mtb continues to acquire mutations during latency and provide a novel explanation for the observation that isoniazid monotherapy for latent tuberculosis is a risk factor for the emergence of INH resistance.
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影响因子：
64.8
作者：
Denver, DR;Morris, K;Thomas, WK
通讯作者：
Thomas, WK
影响因子：
64.5
作者：
Boshoff, HIM;Reed, MB;Mizrahi, V
通讯作者：
Mizrahi, V
来自南非夸祖鲁 - 纳塔尔省的多种耐药性结核病的基因组分析。
影响因子：
3.7
作者：
Ioerger TR;Koo S;No EG;Chen X;Larsen MH;Jacobs WR Jr;Pillay M;Sturm AW;Sacchettini JC
通讯作者：
Sacchettini JC
影响因子：
7
作者：
Li, Heng;Ruan, Jue;Durbin, Richard
通讯作者：
Durbin, Richard
DOI：
10.1073/pnas.0803466105
发表时间：
2008-07-08
影响因子：
11.1
作者：
Lynch, Michael;Sung, Way;Thomas, W. Kelley
通讯作者：
Thomas, W. Kelley