Dataset Information

Rice Defensin OsAFP1 is a New Drug Candidate against Human Pathogenic Fungi.

ABSTRACT: Fungal infections, such as candidiasis and aspergillosis, are some of the most frequent infections in humans. Although antifungal drugs are available for the treatment of these infections, antifungal agents with new mechanisms of action should be developed because of the increasing incidence of drug-resistant pathogens in recent years. In this study, a basic functional analysis of rice defensin OsAFP1, a novel antifungal drug candidate, was conducted. OsAFP1 exerted fungicidal activity against Candida albicans, the most common pathogenic fungus in humans, at 4??M concentration, but it did not inhibit the growth of human pathogenic bacteria. In addition, OsAFP1 retained structural stability after heat treatment at 100?°C for 10?min and after serum treatment at 37?°C for 24?h. A propidium iodide (PI) uptake assay and mutational analysis revealed that amino acid residues within the C-terminal ?-core motif of OsAFP1, particularly Leu-39 and Lys-41, play an important role in its antifungal activity. Further, PI uptake and apoptosis assays suggested that OsAFP1 exerts its antifungal activity by inducing apoptosis of target cells. Immunohistochemistry showed that the OsAFP1 target molecule was located in the cell wall. These findings indicate that OsAFP1 may be developed into a potent antifungal drug.

SUBMITTER: Ochiai A

PROVIDER: S-EPMC6065317 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Rice Defensin OsAFP1 is a New Drug Candidate against Human Pathogenic Fungi.

Ochiai Akihito A Ogawa Kodai K Fukuda Minami M Ohori Masahiro M Kanaoka Takumi T Tanaka Takaaki T Taniguchi Masayuki M Sagehashi Yoshiyuki Y

Scientific reports 20180730 1

Fungal infections, such as candidiasis and aspergillosis, are some of the most frequent infections in humans. Although antifungal drugs are available for the treatment of these infections, antifungal agents with new mechanisms of action should be developed because of the increasing incidence of drug-resistant pathogens in recent years. In this study, a basic functional analysis of rice defensin OsAFP1, a novel antifungal drug candidate, was conducted. OsAFP1 exerted fungicidal activity against C ...[more]

PMID: 30061724

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Project description:Multifunctional drugs have shown great promise in biomedicine. Organisms with antimicrobial and anticancer activity in combination with antioxidant activity need further research. The Red Sea and the Arabian Gulf coasts were randomly sampled to find fungi with multifunctional activity. One hundred strains (98 fungi and 2 lichenized forms) were isolated from 15 locations. One-third of the isolates inhibited clinical bacterial (Staphylococcus aureus, Bacillus subtilis, Vibrio cholerae, Salmonella typhi, S. paratyphi) and fungal pathogens (Talaromycets marneffei, Malassezia globose, Cryptococcus neoformans, Candida albicans, Aspergillus fumigatus) and four cancer cell lines (Hep G2 liver, A-549 lung, A-431skin, MCF 7 breast cancer). Bacterial and cancer inhibition was often accompanied by a high antioxidant activity, as indicated by the principal component analysis (PCA). PCA also indicated that fungal and bacterial pathogens appeared to be inhibited mostly by different marine fungal isolates. Strains with multifunctional activity were found more from the Rea Sea than from the Arabian Gulf coasts. The highest potential for multifunctional drugs were observed for Acremonium sp., Acrocalymma sp., Acrocalymma africana, Acrocalymma medicaginis (activity reported for the first time), Aspergillus sp. Cladosporium oxysporum, Emericellopsis alkaline, Microdochium sp., and Phomopsis glabrae. Lung, skin, and breast cancers were inhibited 85%–97% by Acremonium sp, while most of the isolates showed low inhibition (ca 20%). The highest antifungal activity was observed for Acremonium sp., Diaporthe hubeiensis, Lasiodiplodia theobromae, and Nannizia gypsea. One Acremonium sp. is of particular interest to offer a multifunctional drug; it displayed both antifungal and antibacterial activity combined with high antioxidant activity (DPPH scavenging 97%). A. medicaginis displayed combined antibacterial, anticancer, and antioxidant activity being of high interest. Several genera and some species included strains with both high and low biological activities pointing out the need to study several isolates to find the most efficient strains for biomedical applications.

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Rice Defensin OsAFP1 is a New Drug Candidate against Human Pathogenic Fungi.

Publications

Rice Defensin OsAFP1 is a New Drug Candidate against Human Pathogenic Fungi.

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