Phytochemical targeting of SASP2-mediated DNA protection to impair spore resilience in Bacillus cereus: A Computational Investigation.

Spore-forming bacteria such as Bacillus cereus pose a significant public health challenge due to their ability to survive harsh environmental conditions, resist conventional decontamination strategies, and cause recurrent infections in clinical and food-associated environments. This persistence is primarily associated with sporulation, a tightly regulated developmental process in which long-term survival depends on maintaining genome integrity while cellular metabolism remains largely inactive. DNA-binding proteins are therefore central to sporulation, as effective DNA condensation and protection are essential for sporulation progression and cyst wall maturation. Among these, α/β-class small acid-soluble proteins (SASPs), particularly SASP2, bind to the DNA minor groove and stabilize the genome during dormancy. In this study, a structural model of the B. cereus SASP2-DNA complex was constructed and analyzed through an integrated computational approach to identify compounds targeting this interaction. Phytochemicals derived from Garcinia mangostana, Garcinia cowa, Ficus exasperata, and Entada abyssinica, previously reported for antimicrobial activity, were evaluated for their potential to interact with the SASP2-DNA interface, a mechanism not previously explored. Several compounds showed strong binding affinity at the SASP2-DNA minor-groove interface and were predicted to influence key interactions under simulated stress conditions, leading to DNA compaction stability and stress tolerance, which may subsequently affect cyst wall formation and spore viability. Notably, the identification of plant-derived compounds capable of targeting the SASP2-DNA interface represents a novel observation. Overall, these findings provide a promising computational basis for exploring strategies to limit the persistence and transmission of B. cereus infections.