Aureobasidin A (AbA) is a novel cyclic depsipeptide antifungal antibiotic. The antifungal activity of AbAwas studied in vitro and in vivo in comparison with clinically effective antifungal agents, amphotericin B and fluconazole. AbAwas highly active in vitro against many pathogenic fungi, including Candida albicans, Cryptococcus neoformans, Blastomyces dermatitidis and Histoplasma capsulatum. The activity was superior to amphotericin B in most cases. AbAexhibited fungicidal action toward growing cultures of C. albicans. It was highly tolerated by mice and showed good efficacy in the treatment of murine systemic candidiasis whengiven orally or subcutaneously. AbA's fungicidal action in mice with candidiasis was more effective than fluconazole and amphotericin B.The incidence of systemic fungal infections are increasing in immunecompromisedpatients with several underlying diseases, such as leukemia and acquired immunodeficiency syndrome (AIDS), and in patients receiving anti-neoplastic agents, immunosuppressive agents or broad spectrum antibacterial antibiotics. Amphotericin B, flucytosine, and two imidazole drugs, miconazole and ketoconazole, have been the drugs of choice for systemic antifungal chemotherapy. Recently, two neworal triazoles, fluconazole and itraconazole,1) have been successfully developed and are now available for the treatment of some systemic fungal infections. However, clinical usefulness of all of these drugs is limited to insufficient therapeutic efficacy and/or toxicity. Thus there is a need for novel antifungal agents with a greater clinical efficacy.Aureobasidin A (AbA) is a new antifungal cyclic depsipeptide antibiotic (Fig. 1) produced by Aureobasidium pullulans R106.2~4) The characteristic of the structure of AbAis that of a peptide composed of eight L-form amino acids linked through one hydroxy acid to form a ring structure. There are some cyclic peptide antibiotics with antifungal activity in vitro, including valinomycin,5) syringomycin,6'7) calophycin8) and aculeacin/echinocandin family.9~1 1} Manyof them effect cell membrane permeability and have toxicity to eukaryotic cells. Several antifungal cyclic peptides with a long-chain fatty acid, such as aculeacin A, echinocandin B and their analogs, inhibit fungal cell wall synthesis with low acute toxicity. 9' 1 0) However, they show a narrow spectrum antifungal activity, ineffectiveness to murine candidiasis when given orally, and hemolytic effect. On the other hand, AbAhas a broader spectrum and higher

Aureobasidins A to R were isolated from the fermentation broth of Aureobasidium pullulans R106. Aureobasidins are cyclic depsipeptide antibiotics with MW's ranging from 1,070 to 1,148. Aureobasidins showed high in vitro antifungal activity against Candida albicans.

It was proved that three spore coat proteins of 48, 36, and 22 kDa (P48, P36, and P22) were the components of the outermost layer (OL) of Bacillus megaterium ATCC 12872 spore by analysis of the isolated OL. And it was indicated that these proteins were deposited not by disulfide bond, but by ionic and/or hydrophobic bonds on the spore. Among them, P36 and P22 were expected to be located on the very surface of the spore by immunological analysis. In the OL deficient mutant of B. megaterium ATCC 12872, MAE05, whose spore was lacking in these OL proteins and galactosamine-6-phosphate polymer, both P36 and P22 were present in the mother cell cytoplasm and deposited on the forespores, but they disappeared with the lysis of mother cells. An OL protein-releasing factor having proteolytic activity was detected in the culture supernatant at the late sporulating stage of both the wild-type and the mutant strains. But the factor could not act on the proteins of the mature spores and the forespores at tin (tn indicates n hr after the end of exponential growth) of the wild-type strain. Moreover, P36 and P22 were found in the spores of a revertant of MAE05 which could form galactosamine-6-phosphate polymer, suggesting that this sugar polymer played the role in protecting the OL proteins against the protease-like substance after the deposition.