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

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 was measured after 0 and 10 days of oxygen depletion. Three independent experiments were performed for each timepoint.