2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
June 4th, 2025
Version: 3
Duke University School of Medicine
microbiology
biorxiv

RNAi epimutations conferring antifungal drug resistance are inheritable

Perez-Arques, C.Open in Google Scholar•Navarro-Mendoza, M. I.Open in Google Scholar•Xu, Z.Open in Google Scholar•Walther, G.Open in Google Scholar•Heitman, J.Open in Google Scholar

Epimutations modify gene expression and lead to phenotypic variation while the encoding DNA sequence remains unchanged. Epimutations mediated by RNA interference (RNAi) and/or chromatin modifications can confer antifungal drug resistance and may impact virulence traits in fungi. However, whether these epigenetic modifications can be transmitted across generations following sexual reproduction was unclear. This study demonstrates that RNAi epimutations conferring antifungal drug resistance are transgenerationally inherited in the human fungal pathogen Mucor circinelloides. Our research reveals that RNAi-based antifungal resistance follows a DNA sequence-independent, non-Mendelian inheritance pattern. Small RNAs (sRNAs) are the exclusive determinants of inheritance, transmitting drug resistance independently of other known repressive epigenetic modifications. Unique sRNA signature patterns can be traced through inheritance from parent to progeny, further supporting RNA as an alternative molecule for transmitting information across generations. Understanding how epimutations occur, propagate, and confer resistance may enable their detection in other eukaryotic pathogens, provide solutions for challenges posed by rising antimicrobial drug resistance, and advance research on phenotypic adaptability and its evolutionary implications.

Similar Papers

biorxiv
Thu Jun 05 2025
Structural analysis of the NifL-NifA complex reveals the molecular basis of anti-activation of nitrogen fixation gene expression in Azotobacter vinelandii
Understanding the molecular basis of regulated nitrogen (N2) fixation is essential for engineering N2-fixing bacteria that fulfill the demand of crop plants for fixed nitrogen, reducing our reliance on synthetic nitrogen fertilizers. In Azotobacter vinelandii and many other members of Proteobacteria, the two-component system NifL-NifA controls the expression of nif genes that encode the nitrogen f...
Batista, M. B.
•
Richardson, J.
•
Webster, M. W.
•
Ghilarov, D.
...•
Dixon, R.
biorxiv
Thu Jun 05 2025
Evaluation of Enterobacterales carrying Acinetobacter-associated blaOXA genes--United States, 2017-2022
Through their ability to hydrolyze carbapenems, Ambler class D beta-lactamases endanger patients by limiting the clinical efficacy of beta-lactam antimicrobials. Further, plasmid-mediated transmission can increase mobility of carbapenemase genes between bacteria and facilitate their spread between patients. In the United States and elsewhere, the plasmid-mediated Ambler class D carbapenemase genes...
Orazi, G.
•
Kent, A. G.
•
Wilmott, N.
•
Berhe, D.
...•
Sabour, S.
biorxiv
Thu Jun 05 2025
Disruption of undecaprenyl phosphate recycling suppresses ampC beta-lactamase induction in Pseudomonas aeruginosa
Beta-lactam antibiotics are widely used to treat bacterial infections, but their efficacy is compromised by resistance mechanisms such as the production of beta-lactamases. In Pseudomonas aeruginosa, the chromosomally encoded beta-lactamase AmpC is the primary mediator of beta-lactam resistance. ampC expression is regulated by the transcription factor AmpR, which responds to intracellular peptidog...
Klycheva, K.
•
Gyger, J.
•
Frund, M.
•
Torrens, G.
...•
Fumeaux, C.
biorxiv
Thu Jun 05 2025
Novel Adomaviruses Associated with Blotchy Bass Syndrome in Black Basses (Micropterus spp.)
Black bass (Micropterus spp.) are the most important warmwater game fishes in the United States. They have high socioeconomic and recreational value and support an important aquaculture industry. Since 2008, fisheries managers have been reporting the observation of hyperpigmented melanistic lesions (HPMLs) on smallmouth bass (M. dolomieu) in different ecoregions of the United States. Similar HPMLs...
Iwanowicz, L. R.
•
Raines, C. D.
•
Young, K. T.
•
Blazer, V. S.
...•
Cornman, R. S.
biorxiv
Thu Jun 05 2025
Early Candida - Oral Tumor Interactions Suggest miRNA-Mediated Regulation of Inflammatory and Tumor-associated processes
When simultaneously present, oral cancer and oral candidiasis are associated with high mortality. Recently, fungi-driven OSCC has emerged as a recognized phenomenon, that is triggered by Candida and sustained by several pro-tumor mechanisms. This study aimed to deepen our understanding and investigate how these mechanisms are regulated at the early stages of fungi-tumor interactions. Post-transcri...
Toth, R.
•
Horvath, M.
•
Naglik, J. R.
•
Gacser, A.
biorxiv
Thu Jun 05 2025
IL-6 Evades KSHV-Mediated Hyperadenylation repression via CRM1-Dependent Nuclear Export.
RNA turnover is critical for regulating cellular homeostasis, with nuclear export representing a key step in mRNA fate. During infection by Kaposi Sarcoma-associated Herpesvirus (KSHV), widespread mRNA decay is mediated by the viral endonuclease SOX, which depletes cytoplasmic transcripts and induces secondary nuclear RNA processing defects. One such defect includes transcript hyperadenylation, wh...
Schultz, S.
•
Miles, J.
•
Dwyer, W.
•
MacVeigh-Fierro, D.
•
Muller, M.
biorxiv
Thu Jun 05 2025
Quantitative Real-Time PCR Detection of Inactivated H5 Avian Influenza Virus in Raw Milk Samples by Miniaturized Instruments Designed for On-Site Testing
Highly pathogenic avian influenza virus (HPAIV) of H5 and H7 subtypes has emerged as one of the most important zoonotic pathogens in the 21st century with significant economic consequences. The recent outbreak of H5N1 avian influenza (AI) in dairy cattle highlighted the importance of early detection in managing and mitigating HPAIV outbreaks. A successful high-speed diagnostic response requires ra...
Hsiao, C.-C.
•
Lin, C.-C.
•
Chen, Y.-M.
•
Cheng, M.-C.
...•
Dai, H.-L.
biorxiv
Thu Jun 05 2025
Investigating Cobalt Corrosion Mechanisms in a Phenazine Producing Bacterium
Microbially induced corrosion (MIC) costs trillions of dollars yearly by damaging metal infrastructure. MIC occurs when microorganisms oxidize solid elemental metals using redox-active metabolites such as phenazines, which create soluble metal ions. Phenazine-mediated corrosion has been well studied for iron. Whether such pathways can solubilize the economically critical metal cobalt through therm...
DeJager, A.
•
Kirkland, A.
•
Hinz, A.
•
McMullin, D. R.
•
Gregoire, D. S.
biorxiv
Thu Jun 05 2025
Novel infection by Mucor hiemalis kills Caenorhabditis hosts through intestinal perforation
The nematode Caenorhabditis elegans has emerged as a popular model system to investigate cell biology and host-pathogen interactions. Presently, C. elegans is studied as a natural host of intracellular pathogens such as microsporidia and Orsay virus along with extracellular bacterial and fungal pathogens. The use of C. elegans as a model in host-pathogen research is limited by the number of natura...
Ni, J.
•
Sowa, J. N.
biorxiv
Thu Jun 05 2025
Differential roles of the type I and II secretion systems for the intracellular ABC141 Acinetobacter baumannii infection, which elicits an atypical hypoxia response in endothelial cells
Acinetobacter baumannii poses a substantial global health threat, causing severe multi-drug-resistant infections in hospitalized patients. Circulating clinical isolates present remarkable diversity, with a proportion capable of establishing a transient intracellular niche suitable for persistence, multiplication, and spread. Yet, it remains unknown which bacterial factors mediate the formation and...
Debruyne, C.
•
Hodge, L.
•
Hokamp, K.
•
Ershova, A. S.
...•
Salcedo, S. P.