Biology subjects

Ramirez, E. A.

Publications and source records attributed to Ramirez, E. A..

3 recordsLinked to original sources

bioRxiv2026

Endosome motility controls light-responsive reproductive development and secondary metabolite production in Aspergillus

Filamentous fungi, such as Aspergillus species, use microtubule transport to move early endosomes. Other cargos, such as peroxisomes and mRNAs, "hitchhike" on early endosomes to move throughout the long hyphae of these organisms. In Aspergillus nidulans, peroxisomes hitchhike on early endosomes using the endosomal protein PxdA and the peroxisomal protein AcbdA. The HookA adaptor protein links endosomes to microtubule motors. Here, we set out to explore the physiological functions of peroxisome hitchhiking and endosome motility. Aspergillus nidulans has a complex life cycle that includes asexual and sexual reproduction. A. nidulans and other fungi within the Pezizomycotina subphylum are also notable for the vast number of secondary metabolites they produce. Light and other environmental conditions influence developmental decisions and secondary metabolite production. Here, we found that sexual reproduction is favored in the absence of endosome motility, even in the light, which normally promotes asexual reproduction. RNA sequencing of strains lacking PxdA-marked motile early endosomes showed altered expression of genes involved in development. Unexpectedly, we also observed altered expression of genes involved in secondary metabolism in strains lacking endosome motility and peroxisome hitchhiking. Using mass spectrometry, we found that the loss of endosome motility affected the biosynthesis of secondary metabolites, including sterigmatocystin, a carcinogenic mycotoxin that is a food contaminant. Finally, in a pathogenic species, Aspergillus fumigatus, we found that deletion of its pxdA homolog also significantly altered secondary metabolite production. Our work uncovers an unexpected link between organelle motility, developmental decisions in response to light, and secondary metabolite production in filamentous fungi.

cell biology↗

bioRxiv2025

Whole-chromosome duplications drive antimicrobial resistance in Aspergillus fumigatus

Aneuploidy causes genome plasticity and enables adaptive responses that increase stress resistance and facilitate persistence under changing conditions in eukaryotes ranging from fungal pathogens to human cancer cells. Aspergillus fumigatus is a soil-resident mold and the most prevalent etiologic agent of invasive fungal infections globally. Invasive aspergillosis has an alarmingly high mortality rate, and fungal persistence in the infection microenvironment often renders treatments unsuccessful. Treatment failures can result from innate or acquired antifungal drug resistance and from fungal adaptation to other stressors encountered during infection including nutrient limitation, immune cell activity, and changes in pH and oxygen tension. Survival under changing environmental and host conditions therefore necessitates an ability to dynamically adapt to stress. We find that exposure of A. fumigatus to FK506, an antifungal and immunosuppressive Streptomyces natural product that inhibits the master regulatory phosphatase calcineurin, selects for unstable whole-chromosome aneuploidies that alleviate the polarized growth defects caused by calcineurin inhibition. Transcriptomic analysis revealed that Chr7 disomy leads to induction of the normally-silent neosartoricin biosynthetic gene cluster in response to FK506 exposure, and we demonstrate that constitutive genetic induction of this cluster is sufficient to largely recapitulate in a haploid background the response to FK506 in the aneuploid state. We further show that aneuploids undergo extensive metabolic rewiring but do not produce detectable neosartoricin, revealing global and cross-pathway effects resulting from both the aneuploid state and activation of nscR. We also demonstrate that the aneuploid chromosome duplications reduce susceptibility to the clinical antifungal voriconazole, underscoring the utility of aneuploidy as a flexible adaptive strategy. These findings represent a major advance in understanding how aneuploidy transiently alters stress responses and metabolism in the deadly human pathogen A. fumigatus. Highlights- A. fumigatus rapidly gains and loses supernumerary chromosomes in response to the calcineurin inhibitor FK506. - Aneuploidy leads to global transcriptional and metabolic rewiring. - Overexpression of the secondary metabolite gene cluster regulator nscR is sufficient to largely recapitulate the aneuploid response to FK506 in a haploid background. - Chr4, 6, and 7 aneuploidies reduce susceptibility to voriconazole without altering expression of the azole target gene cyp51A.

microbiology↗

bioRxiv2024

Biodetection of an odor signature in white-tailed deer associated with infection by chronic wasting disease prions.

Chronic wasting disease (CWD) has become a major concern among those involved in managing wild and captive cervid populations. CWD is a fatal, highly transmissible spongiform encephalopathy caused by an abnormally folded protein, called a prion. Prions are present in a number of tissues, including feces and urine in CWD infected animals, suggesting multiple modes of transmission, including animal-to-animal, environmental, and by fomite. CWD management is complicated by the lack of practical, non-invasive, live-animal screening tests. We previously demonstrated that ferrets were able to detect and discriminate fecal samples from ducks infected or not infected with avian influenza virus based on odor. That work clearly predicted that animal biodetectors can be trained to identify populations and/or individuals infected with CWD via detection of fecal odors. Such a tool may also prove useful in identifying potentially infected live animals, carcasses, urine, feces, and contaminated environments. Toward this goal, dogs were trained to detect and discriminate CWD infected individuals from non-infected deer in a laboratory setting. Dogs were tested with novel panels of fecal samples demonstrating the dogs ability to generalize a learned odor profile to novel odor samples based on infection status. Additionally, dogs were transitioned from alerting to fecal samples to an odor profile that consisted of CWD infection status with a different odor background using different sections of gastrointestinal tracts. These results indicated that canine biodetectors can discriminate the specific odors emitted from the feces of non-infected versus CWD infected white-tailed deer as well as generalizing the learned response to other tissues collected from infected individuals. These findings suggest that the health status of wild and farmed cervids can be evaluated non-invasively for CWD infection via monitoring of volatile metabolites thereby providing an effective tool for rapid CWD surveillance.

animal behavior and cognition↗