Biology subjects

Dabholkar, A.

Publications and source records attributed to Dabholkar, A..

3 recordsLinked to original sources

bioRxiv2025

Role of the osaA transcription factor gene in development, secondary metabolism and virulence in the mycotoxigenic fungus Aspergillus flavus

Aspergillus flavus colonizes oil-seed crops contaminating them with aflatoxins, highly carcinogenic mycotoxins that cause severe health and economic losses. Genetic studies may reveal new targets for effective control strategies. Here we characterized a putative WOPR transcription factor gene, osaA, in A. flavus. Our results revealed that osaA regulates conidiation and sclerotial formation. Importantly, deletion of osaA reduces aflatoxin B1 production, while, unexpectedly, transcriptome analysis indicated upregulation of aflatoxin biosynthetic genes, suggesting post-transcriptional or cofactor-mediated regulation. Cyclopiazonic acid production also decreased in absence of osaA. In addition, the osaA mutant exhibited upregulation of genes in the imizoquin and aspirochlorine clusters. Moreover, osaA is indispensable for normal seed colonization; deletion of osaA significantly reduced fungal burden in corn kernels. Aflatoxin content in seeds also decreased in the absence of osaA. Furthermore, deletion of osaA caused a reduction in cell-wall chitin content, as well as alterations in oxidative stress sensitivity, which could in part contribute to the observed reduction in pathogenicity. Additionally, promoter analysis of osaA-dependent genes indicated potential interactions with stress-responsive regulators, indicated by an enrichment in Sko1 and Cst6 binding motifs. Understanding the osaA regulatory scope provides insight into fungal biology and identifies potential targets for controlling aflatoxin contamination and pathogenicity. Key ContributionAspergillus flavus osaA controls morphological and chemical development, as well as phytopathogenicity, and could be a promising target for a control strategy against A. flavus to reduce health risks and economic losses associated with aflatoxin contamination.

molecular biology↗

bioRxiv2025

Macrophage phagocytosis of Coccidioides promotes its differentiation into the parasitic form

Coccidioides is an endemic fungus that is increasing in prevalence and can cause life threatening disease in otherwise immunocompetent people. In the environment the spores (arthroconidia) develop into hyphae, yet when they are inhaled by a mammalian host, they develop into a unique form called the spherule. The transition to spherule can be triggered in vitro with elevated temperatures and high CO2 levels, but the signals and host cells that might trigger Coccidioides spherulation in vivo are not known. We used live imaging to investigate how macrophages affect the fate of Coccidioides arthroconidia. Under tissue culture conditions, arthroconidia quickly developed into hyphae. The addition of macrophages promoted spherule development and delayed hyphal formation, indicating that innate immune cells can influence Coccidioides development into the pathogenic form. Exposure of arthroconidia to macrophage supernatants was not sufficient to stimulate spherulation, which was dependent on phagocytosis of arthroconidia by macrophages. Transcriptomics analysis of Coccidioides co-cultured with macrophages revealed a signature concordant with spherules grown in vitro and allowed the identification of a core set of spherule-specific transcripts. In addition, we identified Coccidioides transcripts with significantly higher abundance in the presence of macrophages compared to in vitro spherules, suggesting these factors may be needed to survive and thrive in the presence of innate immune cells. This work lays a foundation for uncovering host-pathogen signaling as well as Coccidioides factors that are critical for pathogenesis.

microbiology↗

bioRxiv2023

Role of the osaA gene in Aspergillus fumigatus development, secondary metabolism and virulence.

Aspergillus fumigatus is the leading cause of aspergillosis, associated with high mortality rates, particularly in immunocompromised individuals. In search of novel genetic targets against aspergillosis, we studied the WOPR transcription factor OsaA. Deletion of the osaA gene resulted in colony growth reduction. Conidiation is also influenced by osaA; both osaA deletion and overexpression resulted in a decrease in spore production. Wild-type expression levels of osaA are necessary for expression of the conidiation regulatory genes brlA, abaA and wetA. In addition, osaA is necessary for normal cell wall integrity. Furthermore, deletion of osaA resulted in a reduction in the ability of A. fumigatus to adhere to surfaces, decreased thermotolerance, as well as increased sensitivity to oxidative stress. Metabolomics analysis indicated that osaA deletion or overexpression led to alterations in the production of multiple secondary metabolites, including gliotoxin. This was accompanied by changes in the expression of genes in the corresponding secondary metabolite gene clusters. These effects could be, at least in part, due to the observed reduction in the expression levels of the veA and laeA global regulators when the osaA locus was altered. Importantly, our study shows that osaA is indispensable for virulence in both the neutropenic and corticosteroid-immunosuppressed mouse models.

microbiology↗