Fungal cell wall septation and cytokinesis are inhibited by bleomycins Journal Article

Authors: Moore, C. W.; McKoy, J.; Del Valle, R.; Armstrong, D.; Bernard, E. M.; Katz, N.; Gordon, R. E.
Article Title: Fungal cell wall septation and cytokinesis are inhibited by bleomycins
Abstract: When the essential and distinctive cell walls of either pathogenic or nonpathogenic fungi break, cytoplasmic membranes rupture and fungi die. This fungicidal activity was discovered previously on nonproliferating Saccharomyces cerevisiae cells treated briefly with the oxidative tool and anticancer drug family of bleomycins. The present studies investigated effects of bleomycin on growing fungal organisms. These included the medically important Aspergillus fumigatus and Cryptococcus neoformans, as well as the emerging human pathogen and fungal model, S. cerevisiae. Bleomycin had its highest potency against A. fumigatus. Scanning electron microscopy and thin-section transmission electron microscopy were used to study morphological growth characteristics. Killing and growth inhibition were also measured. Long, thin, and segmented hyphae were observed when A. fumigatus was grown without bleomycin but were never observed when the mold was grown with the drug. Bleomycin arrested conidial germination, hyphal development, and the progression and completion of cell wall septation. Similarly, the drug inhibited the construction of yeast cell wall septa, preventing cytokinesis and progression in the cell division cycle of S. cerevisiae. Even when cytoplasms of mother and daughter cells separated, septation and cell division did not necessarily occur. Bizarre cell configurations, abnormally thickened cell walls at mother-daughter necks, abnormal polarized growth, large undivided cells, fragmented cells, and empty cell ghosts were also produced. This is the first report of a fungicidal agent that arrests fungal growth and development, septum formation, and cytokinesis and that also preferentially localizes to cell walls and alters isolated cell walls as well as intact cell walls on nongrowing cells.
Keywords: drug efficacy; nonhuman; cytology; electron microscopy; microscopy, electron; cell division; culture medium; drug potency; drug effect; physiology; cell wall; saccharomyces cerevisiae; bleomycin; fungus; aspergillus fumigatus; conidium; fungus hyphae; fungi; fungus growth; cytokinesis; growth inhibition; transmission electron microscopy; fungal cell; scanning electron microscopy; microscopy, electron, scanning; cryptococcus neoformans; fungicidal activity; humans; human; priority journal; article; bleomycin a2; bleomycin b2
Journal Title: Antimicrobial Agents and Chemotherapy
Volume: 47
Issue: 10
ISSN: 0066-4804
Publisher: American Society for Microbiology  
Date Published: 2003-10-01
Start Page: 3281
End Page: 3289
Language: English
DOI: 10.1128/aac.47.10.3281-3289.2003
PUBMED: 14506042
PROVIDER: scopus
PMCID: PMC201140
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Donald Armstrong
    109 Armstrong
  2. Edward M Bernard
    25 Bernard