MP-1

Membranolytic peptides are potential cancer therapeutics, although targeting cancer cells specifically remains an unmet challenge. We have modified the membranolytic peptide MP1, from Polybia paulista, to direct its action specifically to some cancer cells, thereby improving its cancer therapeutic characteristics and reducing its nonspecific toxicity. MP1 was modified by addition of sequences allowing binding to the cancer biomarker EGFR, with or without sequences directing cleavage by the cancer biomarker MMP-2. Toxicity was assessed in human breast cell lines and was correlated with EGFR expression and MMP-2 activity. Efficacy as an antitumor agent was assessed in MDA-MB-468 xenograft models. C-terminal addition of targeting sequences generally reduced cellular toxicities of peptides relative to wildtype MP1. Cell lines that retained the highest sensitivities to these fusion peptides expressed the highest EGFR and/or MMP-2 levels, supporting specific cytotoxic activity directed to these biomarkers. Treatment with an MMP-2 inhibitor significantly reduced the cell-killing activity of peptides containing MMP-2 cleavage sites, further supporting specific targeting. Fusion peptides significantly induced apoptosis and reduced survival in EGFR/MMP-2 high cancer cells, while sparing EGFR/MMP-2 low cells in standard tissue culture and 3D-spheroids. Systemic treatment with the EGFR-MMP-MP1 fusion significantly reduced tumor size in MDA-MB-468 xenograft models, confirming in vivo efficacy against cancer cells and acceptable systemic toxicity. We conclude that EGFR-MMP-MP1 peptides represent a novel cancer therapeutic for further development.

Over geologic timescales, the natural weathering of silicate minerals in soils and regolith regulates atmospheric CO 2 . Although this process is slow relative to anthropogenic emissions, several strategies have been proposed to accelerate this process for climate mitigation. These include the application of finely‐ground silicate rock to increase mineral surface area (enhanced weathering, EW) and the use of microbes that catalyze mineral dissolution and CO 2 biomineralization (microbial carbon dioxide mineralization, MCM). While both approaches show promise, their combined application has rarely been tested. Here, we examined how soil chemistry and bacterial communities respond to a basalt feedstock rich in silicate minerals, a Bacillus subtilis strain (MP1) previously shown to enhance weathering, and their combination. In a 91‐day soybean mesocosm experiment with slightly acidic soil (pH 6.6), MP1 persisted where applied, indicating successful inoculation via seed treatment. Basalt amendments had the strongest effect on soil bacterial community composition, whereas inoculation with MP1 exerted a smaller but detectable influence. Biogeochemical indices of weathering indicated that co‐application of basalt and MP1 enhanced carbonate alkalinity beyond basalt alone. Soil carbonate alkalinity increased with MP1 treatment both with and without basalt, while soil pH and cation exchange capacity (CEC) increased with basalt in both MP1 and non‐MP1 treatments. Total carbon was highest in the combined MP1 + basalt treatment, suggesting that MP1 may mitigate short‐term organic carbon losses associated with basalt‐driven priming. Overall, these results provide new insights into interactions between biological and mineral‐based carbon dioxide removal (CDR) strategies, suggesting that co‐application of MP1 with basalt in slightly acidic soil may enhance carbonate alkalinity while reducing organic carbon losses relative to basalt alone. Thus, pairing B. subtilis MP1 with enhanced weathering deployments emerges as a promising strategy to improve CDR efficiency.