GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302156/primaryOK200TranscriptomicsMycobacterium tuberculosisExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302156GEOGSEfalseGrowth arrest of Mycobacterium tuberculosis in acidic environments enhances their survival of antibiotic treatmentThe 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.2026/05/28GSE302156GSM9097193GSM9097195GSM9097194GSM9097197GSM9097196GSM9097199GSM9097210GSM9097198GSM9097212GSM9097201GSM9097211GSM9097200GSM9097214GSM9097203GSM9097202GSM9097213GSM9097216GSM9097205GSM9097204GSM9097215GSM9097207GSM9097206GSM9097209GSM909720827507302156Mycobacterium tuberculosis