Aspergillus giganteus

A. giganteus produces an antifungal protein (AFP) that has potential applications for preventing fungal infection in both pharmaceutical and agricultural settings. AFP has been shown to restrict the growth of numerous economically-important filamentous fungi.[12] These include Aspergillus fumigatus, the main cause of aspergillosis in humans,[12] and other Aspergillus species;[13] Fusarium oxysporum and related Fusarium species,[12] common pathogens of tomato, bean, banana, melon, cotton, and chickpea plants;[14] Magnaporthe grisea, a pathogen of rice and cereal crops;[2] and Botrytis cineara, pathogenic to geranium and other economically important ornamental plants.[15] Additionally, AFP may restrict the growth of the oomycete Phytopthera infestans,[2] the pathogen infamous for causing late blight in potatoes (the main cause of the Great Famine of Ireland) and tomatoes.[16]

In additional to having high potential for success in combatting the infections listed above, AFP does not inhibit the viability of yeast, bacteria, mammalian,[17] or plant cells.[18] Because there are many filamentous fungal species that do not respond to AFP, it is likely that the protein's detrimental effects are species-specific.[13][19] As such, AFP could be used to treat and prevent infection by very specific pathogens without harm to patients or host plants. Furthermore, the protein can be easily synthesized through fermentation of A. giganteus and is resistant to hear. In comparison to other antifungal treatments, small amounts of the protein are needed to prevent the growth of harmful pathogens.[20] In combination with the fact that AFP almost completely blocks growth of sensitive, pathogenic fungi (unlike the ozone, hydrogen peroxide, and chlorine dioxide antifungal treatments currently used in agricultural systems,)[18] these factors highlight AFP's potential as a cheap, mass-producible, and extremely effective solution to pathogen infection.

The cysteine-rich,[20] amphipathic[13] protein inhibits the growth of AFP-senstivie pathogens through multiple pathways. First, AFP may inhibit cell growth by inhibiting chitin synthesis.[12] In sensitive fungi, AFP activates the cell wall integrity pathway, thereby enhancing the expression of the α-1,3-glucan synthase A gene responsible for remodeling cell walls and inhibiting the formation of chitin.[21] AFP may also alter the cell membrane permeability of sensitive fungi,[19] particularly of Aspergillus niger,[13] or cause an immediate, sustained increase in calcium cation cell resting potential that often results in programmed cell death.[21] Each of these pathways ultimately results in the death of the AFP-sensitive pathogen. Although more research is needed to identify how these pathways work in consort, the wide variety of AFP modes of action highlights that the protein may interact with sensitive pathogens in different ways, that these pathogens vary in their susceptibility to AFP.[13]

In preliminary studies on the pharmaceutical and agricultural applications of AFP, researchers used AFP to halt the growth of Phytopthera infestans[2] and Aspergillus species[12][13][19] in culture. In applying AFP solutions to plant leaves and roots, infections by Botrytis cineara in geranium plants[15] and Magnaporthe grisea in rice plants were eliminated.[2] In each of these cases, AFP caused deformations in the hyphae of the sensitive fungi, resulting in reduced hyphal elongation and inability of the pathogen to grow.[2][15] In addition to direct application to plant structures, the AFP-encoding gene can be edited into the genomes of the plants affected by the AFP-sensitive fungi such that the plants are able to synthesize the protein on their own.[22][23][24] This technique has been successfully used to decrease infection by Puccinia substriata, the main cause of rust disease, and Sclerospora graminicola, a causal agent of downy mildew, in pearl millet plants,[22] as well as infection by Magnaporthe grisea in rice plants.[23][24] Although genetic enhancement halted infection in laboratory and greenhouse settings, researchers continue to debate about the scalability of plant genome editing and the ability of plants themselves to synthesize enough AFP to fight off pathogen infection in the field.[23][24]