Pham, L. T. | bioRxiv Science

bioRxiv2025

Plastic-Degrading Clusters of Orthologous Groups in Prokaryotes

Micro- and nanoplastic pollution (MNPP) is an increasing environmental threat due to the persistence, dispersal, and potential toxicity of plastic particles. Although microbial biodegradation offers a sustainable mitigation strategy, a comprehensive understanding of plastic-degrading proteins across microbial taxa is lacking. Here, we present the Plastic-Degrading Clusters of Orthologous Groups (PDCOGs) database (https://phylobone.com/microworld/PDCOG), comprising 625,616 potential plastic-degrading proteins (PPDPs) from free-living prokaryotes organized into 51 orthologous groups. The database/PDCOGs enable systematic analysis of microbial plastic-degrading capacity across ecosystems and phylogenetic lineages. Notably, PPDPs constitute [~]3.5% of all prokaryotic proteins, with over 95% of the species having the potential to biodegrade at least one plastic polymer type. This resource provides a genomic tool/framework for exploring the ecological and evolutionary importance of plastic biodegradation and supports future efforts to mitigate the global MNPP crisis.

microbiology↗

bioRxiv2024

Brilacidin, a novel antifungal agent against Cryptococcus neoformans

Cryptococcus neoformans causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against C. neoformans. BRI is able to affect the organization of the cell membrane, increasing fungal cell permeability. We also investigated the effects of BRI against the model system Saccharomyces cerevisiae by analyzing libraries of mutants grown in the presence of BRI. In S. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism. In vivo experiments show BRI significantly reduces C. neoformans survival inside macrophages and partially clears C. neoformans lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against C. neoformans. BRI+CAS affects endocytic movement, calcineurin, and mitogen activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis. ImportanceInvasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts, Cryptococcus neoformans and Cryptococcus gattii. There are few therapeutic options for treating cryptococcosis and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against C. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI+CAS against C. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.

microbiology↗