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Growth arrest of Mycobacterium tuberculosis in acidic environments enhances their survival of antibiotic treatment

ABSTRACT: The ability of Mycobacterium tuberculosis (Mtb) bacilli to adapt to host microenvironments by changing growth behaviors promotes population-level survival against host and drug stressors. However, we have a poor understanding of how Mtb’s growth behaviors change at a single-cell level as the population responds to host environmental cues. Here we show that Mtb adapts to acidic conditions by increasing the proportion of bacteria in a growth-arrested state rather than uniformly slowing the growth rate of the entire population. Bacteria in the growth-arrested subpopulation were more tolerant to treatment with ethambutol. Clinical strains in both neutral and acidic conditions have a higher proportion of bacteria in the growth-arrested state, suggesting that growth arrest is a bet-hedging mechanism that is important during infection. The PhoPR two-component system is thought to be a master regulator that enables Mtb to adapt to and survive acidic pH stressors, but we show that it is a partial regulator of the non-growing bacterial subpopulation and that other transcriptional regulators are involved. Our study demonstrates that non-growing subpopulations of Mtb provide fitness benefits and are an active adaptation to environmental cues and not a passive consequence of stressors.

ORGANISM(S): Mycobacterium tuberculosis

PROVIDER: GSE302156 | GEO | 2026/05/28

REPOSITORIES: GEO

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