de Hoog, S. | Search bioRxiv

bioRxiv2025

A Novel Sarocladium spinificis Strain Suppresses Coccidioides posadasii Growth: Morphological and Genetic Perspectives

Sarocladium is a diverse fungal genus with implications in both plant and human diseases, exhibiting roles in pathogenicity, endophytism, and biocontrol. This study characterizes two Sarocladium spinificis strains, CA16 (CBS 144516) and CA18 (CBS 144517), isolated from patients initially suspected of having coccidioidomycosis. Morphological, phylogenetic, and genomic analyses confirmed their classification within the Sarocladium genus, closely related to S. spinificis. Both strains exhibited growth at 24{degrees}C and 37{degrees}C, with distinct morphological features. Comparative genomic analysis identified unique orthologous clusters and functional gene families associated with adaptability and potential pathogenicity. Notably, these strains demonstrated enhanced production of secreted proteins, CAZymes, and peptidases, highlighting metabolic versatility. Co-cultivation experiments revealed that S. spinificis strains CA16 and CA18 inhibited the growth of Coccidioides posadasii, suggesting competitive interactions and potential antifungal properties. These findings underscore the ecological and clinical significance of S. spinificis and its impact on microbial communities, advancing our understanding of its diversity, pathogenic potential, and antifungal capabilities. ImportanceAccurate identification and characterization of emerging fungal pathogens are essential for improving diagnosis and treatment. Sarocladium spinificis, though not widely recognized as a human pathogen, exhibits traits suggesting a potential role in opportunistic infections. This study provides the first detailed morphological, phylogenetic, and genomic characterization of clinical S. spinificis isolates, highlighting its ability to survive at body temperature and its antifungal resistance. Additionally, we demonstrate that these strains inhibit Coccidioides posadasii, the agent of Valley fever, suggesting ecological competition or antifungal properties. These findings contribute to understanding fungal interactions in clinical and environmental settings, with implications for fungal pathogenesis and antifungal strategies. By uncovering new aspects of S. spinificis biology, this work expands knowledge of Sarocladium species in human health and lays the foundation for future research on its ecological role, pathogenic potential, and therapeutic applications.

microbiology↗

bioRxiv2019

Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb and reverses HIV-1 latency

A leading pharmacological strategy towards HIV cure requires "shock" or activation of HIV gene expression in latently infected cells with Latency Reversal Agents (LRAs) followed by their subsequent clearance. In a screen for novel LRAs we used fungal secondary metabolites (extrolites) as a source of bio-active molecules. Using orthogonal mass spectrometry (MS) coupled to latency reversal bioassays, we identified gliotoxin (GTX) as a novel LRA. GTX significantly induced HIV-1 gene expression in latent ex vivo infected primary cells and in CD4+ T cells from all aviremic HIV-1+ participants. RNA sequencing identified 7SK RNA, the scaffold of the P-TEFb inhibitory 7SK snRNP complex to be significantly reduced upon GTX treatment of independent donor CD4+T cells. GTX disrupted 7SK snRNP, releasing active P-TEFb, which then phosphorylated RNA Pol II CTD, inducing HIV transcription. Our data highlight the power of combining a medium throughput bioassay, mycology and orthogonal mass spectrometry to identify novel potentially therapeutic compounds.

molecular biology↗