Paralogs with distinct phase behaviors broaden the in vivo stress response range of condensates

Paralogs are widespread, but their physiological roles are often masked by redundancy. H-NS, a nucleoid-associated protein in Gram-negative bacteria, typically coexists with paralogs such as StpA, whose functions have remained obscured due to the lack of strong phenotypes. We demonstrate here that the interaction between H-NS and StpA fine-tunes the physico-chemical properties of heterochromatin-forming condensates. H-NS forms dynamic condensates, while StpA assembles into stable insoluble fibrils. Yet together, the two proteins form heterotypic condensates, whose fluidity and stability are tunable by their relative stoichiometry. By increasing the levels of StpA over H-NS, bacteria increase heterochromatin-associated condensate stability, thus preserving gene repression and optimizing bacterial growth under stress conditions. Structural differences at these protein's dimerization sites help explain their distinct phase behaviors. Our findings reveal a novel paradigm in which paralogs that are positioned at the opposite ends of the phase spectrum can fine-tune condensates to promote survival in fluctuating environments.