Certain non-steroidal anti-inflammatory drugs can inhibit fungal growth, fungal prostaglandin E2 production, and enzyme activation. This study aims to investigate the antifungal effect of nimesulide against pathogenic filamentous fungi and yeast. The experiments detailed below were also designed to investigate whether the action is dependent on E2 fungal prostaglandins. Our data showed that nimesulide exhibited potent antifungal activity, mainly against Trichophyton mentagrophytes (ATCC 9533) and Cryptococcus neoformans with MIC values of 2 and 62 μg/mL, respectively. This drug was also able to inhibit the growth of clinic isolates of filamentous fungi, such as Aspergillus fumigatus, and dermatophytes, such as T. rubrum, T. mentagrophytes, Epidermophyton floccosum, Microsporum canis, and M. gypseum, with MIC values ranging from 112 to 770 μg/mL. Our data also showed that the inhibition of fungal growth by nimesulide was mediated by a mechanism dependent on PGE2, which led to the inhibition of essential fungal enzymes. Thus, we concluded that nimesulide exerts a fungicidal effect against pathogenic filamentous fungi and yeast, involving the inhibition of fungal prostaglandins and fungal enzymes important to the fungal growth and colonization.
- MeSH
- antifungální látky farmakologie MeSH
- Arthrodermataceae účinky léků růst a vývoj metabolismus MeSH
- Aspergillus fumigatus účinky léků růst a vývoj metabolismus MeSH
- Cryptococcus neoformans účinky léků růst a vývoj metabolismus MeSH
- dinoproston antagonisté a inhibitory biosyntéza MeSH
- mikrobiální testy citlivosti MeSH
- sulfonamidy farmakologie MeSH
- Trichophyton účinky léků růst a vývoj metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: This basic research aimed to investigate the effects of the actin inhibitor latrunculin A (LA) on the human pathogen Cryptococcus neoformans, by freeze-substitution (FS) and electron microscopy (EM), to determine whether the actin cytoskeleton can become a new antifungal target for inhibition of cell division. METHODS: Cells treated with LA for 20 h in yeast-extract peptone dextrose medium were investigated by phase-contrast and fluorescent microscopy, FS and transmission EM, counted in a Bürker chamber and the absorbance was then measured. RESULTS: The disappearance of actin patches, actin cables and actin rings demonstrated the response of the cells of C. neoformans to the presence of the actin inhibitor LA. The removal of actin cables and patches arrested proliferation and led to the production of cells that had ultrastructural disorder, irregular morphology of the mitochondria and thick aberrant cell walls. Budding cells lysed in the buds and septa. CONCLUSION: LA exerts fungistatic, fungicidal and fungilytic effects on the human pathogenic yeast C. neoformans.
- MeSH
- aktiny antagonisté a inhibitory MeSH
- antifungální látky farmakologie MeSH
- bicyklické sloučeniny heterocyklické farmakologie MeSH
- buněčná stěna účinky léků metabolismus MeSH
- buněčné dělení účinky léků MeSH
- Cryptococcus neoformans účinky léků metabolismus MeSH
- elektronová mikroskopie metody MeSH
- fluorescenční mikroskopie metody MeSH
- kryptokokóza farmakoterapie metabolismus mikrobiologie MeSH
- lidé MeSH
- mikrofilamenta účinky léků metabolismus MeSH
- proliferace buněk účinky léků MeSH
- thiazolidiny farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cryptococcus neoformans was grown in 96-well microtiter plates sealed by foil which is less than 0.01 % permeable to oxygen. On day 14 of the cultivation, we observed peculiar clusters of small droplike daughter cells arranged around ?4 % of mother cells. The fact that most of the other cells had died indicates that few cells had been able to survive hypoxic conditions and escape the cell-cycle arrest. However, their daughters were unable to separate from them and to continue their proliferation under such conditions.
Growth patterns of Cryptococcus neoformans submerged culture in different culture volumes, intensity of agitation and types of sealing were evaluated to better understand the physiological role of hypoxia response in this yeast. When low intensity agitation was set at high culture volumes and air exchange between the cultivation vessel and external environment was not abolished completely, the cells proliferated slowly but steadily. On the other hand, when the intensity of agitation was high but the vessel was withheld from fresh air supply, the cells first proliferated rapidly, then arrested completely and finally died. Therefore, the central strategy of C. neoformans here seems to lie in its proliferation-rate adjustment to the available oxygen levels and not in its capacity to survive under anoxia. The data support the opinion that the cultures grown under limited aeration (even though not completely withheld from fresh air supply) are much closer to the real cryptococcal life in human tissues than conventional well-aerated exponential cultures.
- MeSH
- Candida izolace a purifikace klasifikace metabolismus MeSH
- Cryptococcus neoformans izolace a purifikace metabolismus MeSH
- dítě MeSH
- dospělí MeSH
- finanční podpora výzkumu jako téma MeSH
- infekce dýchací soustavy diagnóza epidemiologie mikrobiologie MeSH
- kojenec MeSH
- lidé MeSH
- mykózy epidemiologie mikrobiologie MeSH
- nazofarynx mikrobiologie MeSH
- novorozenec MeSH
- prevalence MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- MeSH
- Cryptococcus neoformans izolace a purifikace metabolismus růst a vývoj MeSH
- dítě MeSH
- dospělí MeSH
- incidence MeSH
- kojenec MeSH
- kryptokokóza epidemiologie mikrobiologie MeSH
- kultivační média MeSH
- lidé středního věku MeSH
- lidé MeSH
- novorozenec MeSH
- oportunní infekce mikrobiologie MeSH
- prevalence MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- senioři MeSH
- ženské pohlaví MeSH
