Nutrient-dependent bet-hedging between reproduction and sporulation in Bacillus subtilis

To thrive in nature, bacteria must constantly balance growth with long-term survival in response to nutrient availability. Although sporulation in Bacillus subtilis is a classical survival strategy, how the sporulation program is regulated by nutrient conditions during exponential growth remains elusive. Here we show that the Spo0A-mediated sporulation program is strongly modulated during exponential phase across different carbon sources and is accompanied by pronounced population heterogeneity on poor carbons. We further identify the transition-state regulator AbrB as a key modulator that integrates growth and sporulation, promoting growth under favorable conditions while facilitating sporulation under poor nutrients. On good carbon sources, AbrB optimizes cellular resource allocation by directly suppressing the unnecessary expression of adaptive pathways. In contrast, on poor carbon sources, where the Spo0A-signaling pathway is strongly activated, AbrB promotes sporulation by repressing the expression of a plasmid-encoded Rap-family phosphatase gene, which otherwise interferes with the Spo0A signaling pathway. Together, these findings reveal a dual-control strategy that fine-tunes the trade-off between growth and survival and promotes bet-hedging under poor growth conditions, with important implications for both fundamental biology and synthetic biology.