Survival of hypoxia-induced dormancy is not a common feature of all strains of the Mycobacterium tuberculosis complex I

While persistence in a dormant state is crucial for the life cycle of Mycobacterium tuberculosis, no investigation regarding dormancy survival of different strains across different lineages was performed so far. We analyzed responses to oxygen starvation and recovery in terms of growth, metabolism and transcription. All different strains belonging to the (Euro-American) lineage (L4) showed similar survival and resuscitation characteristics. Different clinical isolates from the Beijing (L2) , East African-Indian (L3), and Delhi/Central Asian (L1) did not survive oxygen starvation. We show that dormancy survival is lineage-dependent. Recovery from O2 starvation was observed in Euro-American (L4) but no other used strains (L1, L2, L3). Thus, resuscitation from dormancy after oxygen starvation is not a general feature of all M. tuberculosis strains as thought before. Our findings are of key importance to understand infection dynamics of non-Euro American vs Euro American strains and to develop drugs targeting the dormant state. Hypoxia-induced gene expression of M. tuberculosis H37Rv and Beijing was measured after 10 days of oxygen depletion. Three independent experiments were performed for each timepoint.

休眠状态下的持续存活对结核分枝杆菌（Mycobacterium tuberculosis）的生命周期至关重要，但迄今为止尚未有针对不同谱系下不同菌株的休眠存活情况开展的相关研究。本研究从生长、代谢与转录层面，分析了菌株对氧饥饿胁迫及其恢复过程的响应。所有属于欧美（Euro-American）谱系（L4）的菌株均表现出相似的存活与复苏特性；而来自北京系（L2）、东非-印度系（L3）以及德里/中亚系（L1）的临床分离株均无法在氧饥饿胁迫下存活。本研究证实，休眠存活能力具有谱系依赖性：仅欧美谱系（L4）菌株可从氧饥饿胁迫中恢复，其余受试菌株均无此能力。因此，氧饥饿胁迫后的休眠复苏并非如此前所认为的那样，是所有结核分枝杆菌菌株共有的普遍特性。本研究结果对于解析非欧美谱系与欧美谱系菌株的感染动态差异，以及开发靶向休眠状态的抗结核药物具有重要意义。本研究在氧剥夺10天后，对结核分枝杆菌H37Rv与北京系菌株的缺氧诱导基因表达水平进行了检测；每个时间点均设置三次独立生物学重复。