Date of Award:

5-2013

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Biology

Committee Chair(s)

Jon Y. Takemoto

Committee

Jon Y. Takemoto

Abstract

More than 90% of crop diseases are due to fungal infections, which globally cause enormous economic losses. Fungal infections in humans and animals have also become a serious concern, especially in immunocompromised individuals. However, only a few new fungicides have been introduced since the mid-1980s, and concerns with inconsistent and declining effectiveness due to resistance, environmental impacts, animal and human toxicity, and costs continue to challenge the use of available fungicides. There is a serious and persistent need for new antifungal agents that are more effective, eco-friendly, less toxic, and available at reasonable cost.

This study reveals two novel aminoglycosides, FG08 and K20, that are synthesized from kanamycin B and A, respectively. Kanamycin B and A are aminoglycoside antibiotics that kill bacteria. In contrast, FG08 and K20 showed broad-spectrum antifungal activities against a wide range of agriculturally and clinically important fungal pathogens, but they did not inhibit bacteria. They showed no or lowered toxicities against animal cells at their antifungal minimum inhibitory concentrations (MICs). They inhibit fungi by interacting with the fungal plasma membrane, leading to pore formation. K20 can be produced on a large scale, which makes it feasible to develop as a fungicide for commercial application. Additionally, K20 showed synergistic antifungal interaction with azoles against various fungi. Azoles are today’s most widely used antifungal agents to treat fungal infections in agriculture and medicine. In conclusion, this research has helped discover a new class of broad spectrum fungicides, which appear attractive for application as crop disease protectants and therapeutics against serious fungal infections in immunocompromised humans.

Checksum

a47bc4bc28d363b42287cc7146c57e68

Download

Included in

Biology Commons

Share

COinS

Copyright for this work is retained by the student. If you have any questions regarding the inclusion of this work in the Digital Commons, please email us at .