Biology subjects

Acharya, T.

Publications and source records attributed to Acharya, T..

3 recordsLinked to original sources

bioRxiv2026

Candidozyma auris utilizes transferrin, but not heme-bound iron for in vivo virulence

Candidozyma auris (C. auris) is an emerging multidrug-resistant fungal pathogen, and its dissemination to the bloodstream and deep-seated organs is associated with high mortality. The limited antifungal armory and pipelines against C. auris pose a major challenge in disease management. Addressing this threat requires a deeper understanding of fungal virulence mechanisms that promote persistence and of host factors that drive susceptibility. Previous in vitro studies showed that iron enhances C. auris resistance to azoles and echinocandins, whereas iron chelation mitigates this effect. Here, we demonstrate that C. auris does not utilize cell-free heme or induce hemolysis but instead extracts and uses iron from transferrin to support growth and virulence. Deletion of the SIT1 siderophore transporter in C. auris attenuated fungal growth and reduced renal injury, while increased transferrin-iron saturation worsened disease outcomes in immunocompetent mice, highlighting the importance of transferrin-bound iron uptake. Mechanistically, C. auris exploits transferrin-bound iron to enhance ergosterol biosynthesis and activate antioxidant defenses, promoting resistance to neutrophil- and caspofungin-mediated killing. These findings identify elevated transferrin saturation as a novel host susceptibility risk factor for disseminated C. auris infection and reveal how iron availability reshapes fungal physiology to drive infection persistence.

microbiology↗

bioRxiv2024

Essential role of Hepcidin in host resistance to disseminated candidiasis

Candida albicans is a leading cause of life-threatening invasive infections with up to 40% mortality rates in hospitalized individuals despite antifungal therapy. Patients with chronic liver disease are at an increased risk of candidemia, but the mechanisms underlying this susceptibility are incompletely defined. One consequence of chronic liver disease is attenuated ability to produce hepcidin and maintain organismal control of iron homeostasis. To address the biology underlying this critical clinical problem, we demonstrate the mechanistic link between hepcidin insufficiency and candida infection using genetic and inducible hepcidin knockout mice. Hepcidin deficiency led to unrestrained fungal growth and increased transition to the invasive hypha morphology with exposed 1,3, {beta}-glucan that exacerbated kidney injury, independent of the fungal pore-forming toxin candidalysin in immunocompetent mice. Of translational relevance, the therapeutic administration of PR-73, a hepcidin mimetic, improved the outcomes of infection. Thus, we identify hepcidin deficiency as a novel host susceptibility factor against C. albicans and hepcidin mimetics as a potential intervention.

microbiology↗

bioRxiv2019

Transient Receptor Potential Ankyrin1 channel is endogenously expressed in T cells and regulates immune functions

Transient Receptor Potential channel subfamily A member 1 (TRPA1) is a non selective cationic channel, identified initially as a cold sensory receptor. TRPA1 responds to diverse exogenous and endogenous stimuli associated with pain and inflammation. However, the role of TRPA1 towards T cell responses remains scanty. In this work, we explored the endogenous expression of TRPA1 in T cells. By RT-PCR we confirmed the expression of TRPA1 in T cell at RNA level. Using confocal microscopy as well as flow cytometry, we demonstrated that TRPA1 is endogenously expressed in primary murine splenic T cells as well as in primary human T cells. The endogenous expression of TRPA1 is confirmed by using another antibody. TRPA1 was primarily located at the cell surface. TRPA1-specific activator namely AITC increases intracellular Ca2+-levels while two different inhibitors namely A-967079 as well as HC-030031 reduce intracellular Ca2+-levels in T cells. Such Ca2+-influx can also be influenced by chelation of intracellular Ca2+ as well as extracellular Ca2+. TRPA1 expression was found to be increased during CD3/CD28 (TCR) or ConA driven stimulation in T cells. TRPA1-specific inhibitor treatment prevented induction of CD25, CD69 in ConA/TCR stimulated T cells and secretion of cytokines like TNF, IFN-{gamma} and IL-2 suggesting that endogenous activity of TRPA1 may be involved in T cell activation. Collectively these results may have implication in T cell-mediated responses and possible role of TRPA1 in immunological disorders.

immunology↗