Terranova, R. | bioRxiv Science

bioRxiv2025

Functional auxin signaling and phosphorus acquisition triggered in planta by the extremophile bacterium Pseudomonas extremaustralis

Pseudomonas extremaustralis 14-3b, a strain isolated from Antarctica, was evaluated for plant-growth-promoting traits under different oxygen conditions. Genomic analysis revealed genes related to phosphorus solubilization and indole-3-acetic acid (IAA) biosynthesis. In vitro assays confirmed its ability to solubilize tricalcium phosphate and produce gluconic acid. IAA production was higher under microaerobic conditions compared to aerobic cultures. Using Arabidopsis thaliana DII-VENUS reporter lines, we confirmed in vivo IAA perception in roots, with reduced VENUS fluorescence upon bacterial inoculation, regardless of prior oxygen conditions. Confocal microscopy showed root surface colonization and internal localization in cotyledons, including sub-stomatal spaces. Morphological changes in A. thaliana included reduced primary root length and increased root hair length. In wheat, P. extremaustralis exhibited chemotaxis toward root exudates and colonized root tissues. After 30 days in pot experiments, inoculated wheat plants showed significantly higher stem dry weight and leaf phosphorus content than control plants. These findings indicate that P. extremaustralis promotes plant growth through multiple mechanisms, supporting its potential as a bioinoculant under variable environmental conditions, including low oxygen availability.

microbiology↗

bioRxiv2019

In-Depth Characterization and Validation in BRG1-Mutant Lung Cancers Define Novel Catalytic Inhibitors of SWI/SNF Chromatin Remodeling

Members of the ATP-dependent SWI/SNF chromatin remodeling complexes are among the most frequently mutated genes in cancer, suggesting their dysregulation plays a critical role. The synthetic lethality between SWI/SNF catalytic subunits BRM/SMARCA2 and BRG1/SMARCA4 has instigated great interest in targeting BRM. Here we have performed a critical and in-depth investigation of novel dual inhibitors (BRM011 and BRM014) of BRM and BRG1 in order to validate their utility as chemical probes of SWI/SNF catalytic function, while obtaining insights into the therapeutic potential of SWI/SNF inhibition. In corroboration of on-target activity, we discovered compound resistant mutations through pooled screening of BRM variants in BRG1-mut cancer cells. Strikingly, genome-wide transcriptional and chromatin profiling (ATAC-Seq) provided further evidence of pharmacological perturbation of SWI/SNF chromatin remodeling as BRM011 treatment induced specific changes in chromatin accessibility and gene expression similar to genetic depletion of BRM. Finally, these compounds have the capacity to inhibit the growth of tumor-xenografts, yielding important insights into the feasibility of developing BRM/BRG1 ATPase inhibitors for the treatment of BRG1-mut lung cancers. Overall, our studies not only establish the feasibility of inhibiting SWI/SNF catalytic function, providing a framework for SWI/SNF therapeutic targeting, but have also yielded successful elucidation of small-molecule inhibitors that will be of importance in probing SWI/SNF function in various disease contexts.

cancer biology↗