“…Preparation buds, shown light microscopically by staining with methylene blue, and the severe damage such as waving and disruption of the cell membrane, shown electron microscopically, are in accordance with previous findings that this antibiotic exhibited fungicidal action only when cells were growing (10). The high sensitivity of buds to the action of benanomicin A may be due to the fragile structure of rapidly growing cells, in which a delicate balance of synthesis and hydrolysis of the cells is easily disturbed by binding with the antibiotic.…”
The effects of benanomicin A, a mannose‐binding antifungal antibiotic, on yeast cells of Saccharomyces cerevisiae were studied by electron microscopy. Cytological studies using vital stain with methylene blue demonstrated that benanomicin A at 20 and 80 μg/ml killed buds in preference to parent cells. In confirmation, examination by TEM revealed that benanomicin A at 80 μg/ml damaged buds more severely than parent cells. The major effect on the ultrastructure was characterized by severe damage to the cell membrane. In addition, it caused expansion and vacuolation of the endoplasmic reticulum (ER), and partial fragmentation and disappearance of nuclear membranes. The membrane‐disruptive activity of benanomicin A may be closely associated with its membrane affinity.
“…Preparation buds, shown light microscopically by staining with methylene blue, and the severe damage such as waving and disruption of the cell membrane, shown electron microscopically, are in accordance with previous findings that this antibiotic exhibited fungicidal action only when cells were growing (10). The high sensitivity of buds to the action of benanomicin A may be due to the fragile structure of rapidly growing cells, in which a delicate balance of synthesis and hydrolysis of the cells is easily disturbed by binding with the antibiotic.…”
The effects of benanomicin A, a mannose‐binding antifungal antibiotic, on yeast cells of Saccharomyces cerevisiae were studied by electron microscopy. Cytological studies using vital stain with methylene blue demonstrated that benanomicin A at 20 and 80 μg/ml killed buds in preference to parent cells. In confirmation, examination by TEM revealed that benanomicin A at 80 μg/ml damaged buds more severely than parent cells. The major effect on the ultrastructure was characterized by severe damage to the cell membrane. In addition, it caused expansion and vacuolation of the endoplasmic reticulum (ER), and partial fragmentation and disappearance of nuclear membranes. The membrane‐disruptive activity of benanomicin A may be closely associated with its membrane affinity.
“…Pradimicin A also showed fungicidal effects against pulmonary candidiasis and aspergillosis, vaginal candidiasis, and skin Trichophyton mentagrophytes infection in mice with intravenous or topical treatment (177). The antifungal activity of this family of nonribosomal peptides recognizes D-mannose in a manner similar to that for lectins in the presence on calcium (179, 180), ultimately leading to cell death (181). In S. cerevisiae pradimicin A induced an apoptosis-like cell death through ROS accumulation (182).…”
Invasive fungal infections in humans are generally associated with high mortality, making the choice of antifungal drug crucial for the outcome of the patient. The limited spectrum of antifungals available and the development of drug resistance represent the main concerns for the current antifungal treatments, requiring alternative strategies. Antimicrobial peptides (AMPs), expressed in several organisms and used as first-line defenses against microbial infections, have emerged as potential candidates for developing new antifungal therapies, characterized by negligible host toxicity and low resistance rates. Most of the current literature focuses on peptides with antibacterial activity, but there are fewer studies of their antifungal properties. This review focuses on AMPs with antifungal effects, including their in vitro and in vivo activities, with the biological repercussions on the fungal cells, when known. The classification of the peptides is based on their mode of action: although the majority of AMPs exert their activity through the interaction with membranes, other mechanisms have been identified, including cell wall inhibition and nucleic acid binding. In addition, antifungal compounds with unknown modes of action are also described. The elucidation of such mechanisms can be useful to identify novel drug targets and, possibly, to serve as the templates for the synthesis of new antimicrobial compounds with increased activity and reduced host toxicity.
“…Moreover, benanomicin A showed antiviral activities [6,7]. The mechanism of action of benanomicin A was deduced to bind to fungal cell wall, but it has not been confirmed clearly [8,9]. On the other hand, pradimicins were found as antifungal compounds at almost the same time of the discovery of benanomicins [10ϳ12].…”
Benanomicins were found as antifungal antibiotics from the culture of an actinomycete with potent antifungal activities in vitro and in vivo. We aimed to generate derivatives superior to benanomicin A by biotransformation using Escherichia coli constructed with bacterial P450 expression system. We found transformation of benanomicin A into two derivatives, 10-hydroxybenanomicin A and 11-O-demethylbenanomicin A by one of the P450-expressed strains which harbored a plasmid carrying a CYP105C1-homologous gene. Unexpectedly, the biotransformed compounds showed weak antifungal activities in vitro compared with those of benanomicin A.
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