Poster abstracts
Poster number 14 submitted by Hari Krishnan Balasubramanian
2-AAPA-induced redox imbalance causes global reprogramming of multiple cellular organelles, through interaction with putative targets in addition to glutathione reductase
Hari Krishnan Balasubramanian (Molecular, Cellular and Developmental Biology, OSU), Stephen A Osmani (Department of Molecular Genetics, OSU)
Abstract:
Fungal biofilms have unique characteristics including the presence of an extracellular matrix and resistance to anti-fungal drugs as well as the host immune system. Biofilms, having a hypoxic microenvironment similar to that of tumors, also provide a unique opportunity to understand the mechanism of cell growth and survival in hypoxic/nutrient deprived conditions. Current understanding of the cell biology of biofilm forming cells is limited. A recent study from our lab demonstrated that Aspergillus nidulans biofilm founder cells disperse their microtubules (MTs) in response to self-generated hypoxia 1 as biofilms mature. In preliminary data the glutathione reductase inhibitor 2-AAPA was also found to cause dispersal of microtubules, but at a much lower concentration than reported for mammalian cells, indicating potential redox regulation in fungal biofilms. To determine if redox regulation has a role in biofilm formation and maturation, we deleted glutathione reductase A (ΔGlrA), a target of 2-AAPA. The ΔGlrA strain was found to be temperature sensitive but with similar susceptibility to 2-AAPA mediated MT disassembly as compared to wild type (WT). The thioredoxin system was also reported to be a target of 2-AAPA, and a strain harboring a loss of function mutation in thioredoxin (sE15) was also found to be similarly susceptible to MT disassembly caused by 2-AAPA as WT. Losing both glutathione and thioredoxin systems is lethal, but using the heterokaryon rescue technique, we found the double mutant to have similar susceptibility to MT disassembly caused by 2-AAPA as the WT, indicating the existence of novel additional targets for 2-AAPA. The changes induced by 2-AAPA to mitochondria also mimics mitochondrial modifications observed during early biofilm formation. Future work will focus on identifying the factors that play a role in regulation of mitochondrial structure modification during biofilm formation.
References:
1. Shukla, N., Osmani, A. H., and Osmani, S. A. (2017). Microtubules are Reversibly depolymerized in response to changing gaseous microenvironments within Aspergillus nidulans biofilms. Molecular Biology of the Cell, 28(5), 634-644. doi:10.1091/mbc.e16-10-0750
Keywords: Biofilm, Hypoxia, GlrA