Inorganic polyphosphate (iPolyP) is a ubiquitous molecule composed of a variable number of orthophosphate units. Recent studies have highlighted its involvement in colorectal cancer (CRC) cell proliferation. However, further investigations are needed to elucidate its role in CRC cell progression and migration, as well as its influence on the tumor microenvironment. This study focuses on the inorganic polyphosphate (iPolyP)/transient receptor potential cation channel subfamily M member 8 (TRPM8) axis and its impact on CRC progression. To investigate these issues, western blotting, fixed and live cells immunofluorescence, 2D and 3D cell culture on CRC-patient derived tissues, ELISA, and wound healing assays were performed. Our results show that inorganic polyphosphate induces the expression of epithelial-to-mesenchymal transition (EMT) markers in CRC cells. Furthermore, the iPolyP/TRPM8 axis indirectly promotes tumor growth through activation of the Nucleotide-binding oligomerization domain, Leucine-rich Repeat and Pyrin domain-containing protein 3 (NLRP3) inflammasome in immune cells, leading to increased levels of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the tumor microenvironment (TME), thereby advancing CRC. These findings suggest that targeting the iPolyP/TRPM8 pathway may be a promising strategy to inhibit CRC progression and metastasis.

Intensive use of synthetic fungicides to control grapevine downy mildew raises interconnected concerns for human health, environmental safety, and food quality—a challenge that biological control agents (BCAs) are well positioned to address. Among bacterial BCAs, Bacillus velezensis shows strong biocontrol potential, but efficacy varies substantially among conspecific strains, complicating rational strain selection. Whole-genome comparative analysis of two strains with contrasting efficacy against Plasmopara viticola (BLG_B2 and BLG_B4) identified four HIGH-impact variants present exclusively in the ineffective strain BLG_B2, predicted to cause loss of function of glycerol kinase (glpK), the antimicrobial peptide resistance regulator yxdJ, a c-di-GMP phosphodiesterase, and the ribonuclease yeeF. In other Bacillus strains, three of these genes are linked to surfactin biosynthesis, antimicrobial peptide detoxification and the motility-to-biofilm transition; they are therefore proposed as candidate determinants of the biocontrol deficit of BLG_B2, whose causal role remains to be tested. These results show that whole-genome comparison of conspecific BCA strains can generate testable hypotheses on the genomic basis of differential biocontrol efficacy.