|Kim, Jong Heon|
|Haff, Ronald - Ron|
|FARIA, NATALIA C. - New University Of Lisbon|
|MARTINS, M. DE - New University Of Lisbon|
|Chan, Kathleen - Kathy|
|CAMPBELL, BRUCE - Retired ARS Employee|
Submitted to: Molecules
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/22/2013
Publication Date: 7/25/2013
Publication URL: http://handle.nal.usda.gov/10113/58703
Citation: Kim, J.H., Haff, R.P., Faria, N.G., Martins, M.L., Chan, K.L., Campbell, B.C. 2013. Targeting the mitochondrial respiratory chain of Cryptococcus through antifungal chemosensitization: a model for control of non-fermentative pathogens. Molecules. 18:8873-8894 DOI:10.3390/molecules 18088873.
Interpretive Summary: Fungal infection occurring in agricultural farms or humans is a continuously expanding as global issues. This expansion is mainly associated with development of resistance to antifungal drug. Consequently, there is persistent need to enhance the effectiveness of conventional antimycotic drugs or discover and develop new one. In this report, we show that selected phenolic compounds could enhance the antifungal potency of strobilurin, a potent inhibitor of mitochondrial function, against fungal pathogens. Co-application of phenolic compounds and strobilurin negatively affects the common cellular target, resulting in increased sensitivity of fungi. Results of this study will lead to prevention of fungal tolerance to conventional fungicides, such as strobilurins. It will also lower costs or dosages of commercial fungicides required for effective control of fungal pathogens.
Technical Abstract: Enhanced control of species of Cryptococcus, non-fermentative yeast pathogens, was achieved by chemosensitization through co-application of certain compounds with a conventional antimicrobial drug. The species of Cryptococcus tested showed higher sensitivity to mitochondrial respiratory chain inhibition compared to species of Candida. This higher sensitivity results from the inability of Cryptococcus to generate cellular energy through fermentation. To heighten disruption of cellular mitochondrial respiratory chain, octyl gallate or 2,3-dihydroxybenzaldehyde, phenolic compounds inhibiting mitochondrial functions, were selected as chemosensitizers to strobilurin (an inhibitor of mitochondrial respiratory chain). Octyl gallate and/or 2,3-dihydroxybenzaldehyde show potential to serve as antifungal chemosensitizers that in combination with strobilurin greatly enhance antifungal activity. This capacity was shown to be most effective against Cryptococcus, etiologic agents for the leading cause of death among those suffering from immunocompromised disorders. Therefore, chemosensitizers, especially those proven to be safe compounds, such as natural phenolic agents or their structural derivatives, could serve as potential “leads” against yeast pathogens for more effective treatment of mycoses using mitochondrial respiratory chain-inhibitory drugs.