Condition‐dependent resource allocation strategy governed by CodY regulator in <i>Bacillus subtilis</i>

To thrive in nature, bacteria have to rapidly proliferate in favorable conditions while constantly adapt to the fluctuating nutrient environments. However, the molecular players that ensure rapid growth of bacteria in favorable conditions remain poorly understood. Here, we focus on the growth physiology of <i>Bacillus subtilis</i> and find that <i>codY</i> knockout strongly compromises cell growth in rich medium. Global proteome allocation analysis has shown that <i>codY</i> knockout causes a "waste" of cellular resources by stimulating unnecessary expression of many proteins, further reducing the cellular investment on translation machinery. Therefore, CodY-dependent repression is crucial in ensuring rapid growth of <i>B. subtilis</i> in rich medium. On the other hand, the relief of CodY-dependent repression could promote the bacterial adaption during transition from rich medium to minimal medium by shifting resource allocation from ribosome synthesis to amino acid biosynthesis. In addition, the relief of CodY-dependent repression in minimal medium also stimulates pathways of alternative functions such as motility and biosynthesis of secondary metabolites. Our study has thus revealed the pivotal role of CodY in bacterial growth control via governing the condition-dependent resource allocation of <i>B. subtilis</i>, further shedding light on the fundamental molecular strategy of bacteria to achieve fitness maximization.