Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 7/28/2015
Publication Date: 9/10/2015
Citation: Kim, J.H., Chan, K.L., Cheng, L.W. 2015. Targeted antifungal intervention via chemo-biological approaches: Maintaining microbiome dynamics. Meeting Abstract. Poster No. 4.
Technical Abstract: The mycobiome, namely the fungal microbiome, plays an important role in human health by maintaining the dynamics of the overall microbiome. Therefore, strategies to overcome the outgrowth of fungi or to prevent their transition from commensals to pathogens are crucial for public health. Considering the complex link between the mycobiome and other biomes, antifungal intervention strategies having effects only on targeted species are highly desirable. Control of infective fungi, e.g., causative agents for aspergillosis, candidiasis, cryptococcosis or producers of toxic secondary metabolites, is problematic as effective antimycotic agents are often very limited. Moreover, the expansion of fungal resistance to commercial drugs is a global human health issue. Consequently, there is persistent need to enhance the effectiveness of conventional antimycotic agents or discover/develop new intervention strategies. Resistance of fungal pathogens to antimycotic agents frequently involves mutations triggered by environmental stressors. In fungi, stress signals resulting from oxidative/cell wall stress are integrated into the upstream mitogen-activated protein kinase (MAPK) signalling pathways that regulate genes countering the stress. Of note, mutations in MAPK signalling system result in fungal tolerance to antimycotic agents. Many natural compounds are promising antimycotic agents/leads due to their ability to disrupt fungal defense response systems. Furthermore, natural compounds could serve as chemical probes to identify new antifungal mechanisms of action (MOA). In a chemo-biological platform to achieve targeted antifungal intervention, the model yeast Saccharomyces cerevisiae served as a functional tool for identifying MOA of redox-active/cell wall disrupting agents. This also enabled the discovery of new utility for known compounds or the utilization of the natural compounds as chemosensitizing agents to enhance the efficacy of conventional antimycotic agents. Collectively, chemo-biological approaches lead to the development of novel intervention strategies, which enhance the drug susceptibility of targeted fungi, overcome fungal tolerance to conventional drugs, and ensure the maintenance of microbiome dynamics.