Travert, C. | bioRxiv Science

bioRxiv2025

Intracellular amorphous calcium carbonate biomineralization in methanotrophic gammaproteobacteria was acquired by horizontal gene transfer from cyanobacteria

Some bacteria genetically control the biomineralization of intracellular amorphous calcium carbonates (iACC) with potential implications for microbial physiology, evolution, bioremediation and biogeochemical cycling. Until now, this capacity has been documented in Cyanobacteria, the giant gammaproteobacterium Achromatium and a few magnetotactic Pseudomonadota and Nitrospirota. Here, we report the discovery of iACC biomineralization in members of the Methylococcaceae, a family of aerobic methanotrophic Gammaproteobacteria. A homolog of the ccyA gene, previously considered a diagnostic marker for iACC formation in Cyanobacteria, was identified in several Methylococcaceae genomes, based on a search of the conserved C-terminal (GlyZip)3 domain of the encoded calcyanin protein, with a sequence coverage higher than 60% and an E-value lower than 1e-20. Moreover, two cultivated strains, Methylococcus geothermalis and Methylococcus mesophilus, whose genomes contained the ccyA gene, were consistently shown to form iACC granules. The ccyA genes of Methylococcaceae and Microcystis share higher sequence similarity (47%) than with other Cyanobacteria (around 30%) within their common (GlyZip)3 domain, suggesting horizontal gene transfer (HGT) from an ancestral Microcystis-like cyanobacterium to Methylococcaceae. This finding extends the known taxonomic distribution of ccyA and suggests that the capability to biomineralize iACC was acquired by HGT, possibly in environments such as those close to the oxyclines of lakes, where Cyanobacteria and Methylococcaceae commonly co-exist. The discovery of iACC in methane-oxidizing Methylococcaceae highlights a previously unrecognized coupling between calcium carbonate biomineralization and methane cycling in aquatic environments, suggesting that iACC formation may play an overlooked role in microbial carbon storage and local geochemical regulation.

microbiology↗

bioRxiv2024

MDM2 stabilization of Notch intracellular domain upon DNA damage plays a major role in non-small cell lung carcinoma response to platinum chemotherapy

Despite major advances in lung cancer clinical management, majority of patients suffering non-small cell lung carcinoma (NSCLC) are treated in first line with platinum in combination with immune checkpoint inhibitors. Although platinum compounds normally display an initial therapeutic effect, relapse constitutes a major challenge in the clinical management of NSCLC patients. Therefore, it is fundamental to understand the relapse underlying mechanisms to find new therapeutic opportunities to improve patients survival. Here, we found that different DNA damage inducers increase the protein levels of Notch Intracellular Domain (NICD), i.e., the active form of NOTCH1. Mechanistically, we unveiled that upon platinum treatment, there was a concomitant increase of MDM2 together with NICD, and we also observed an MDM2-mediated ubiquitination and stabilization of NICD. Of note, using patient-derived xenografts displaying intrinsic carboplatin resistance, we demonstrated that the combination of carboplatin with MDM2 and NICD inhibitors increased survival and reduced tumor growth compared with carboplatin in monotherapy. Moreover, in patients with NSCLC who received platinum chemotherapy, MDM2 expression level in the tumor was correlated with poor progression-free survival, further validating MDM2 key role in the response to platinum compounds. Our findings open a therapeutic opportunity for NSCLC patients, the main lung cancer subtype of the leading cause of death by cancer worldwide.

cancer biology↗