Derivatisation of metronidazole enhances cytotoxic effect against Acanthamoeba genotype T4 isolates and leads to cytomorphological changes in trophozoites
| Autor: | Miloš Lukáč, Aneta Dušeková, Mária Garajová, Martin Mrva |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genotype Veterinary (miscellaneous) 030231 tropical medicine Acanthamoeba Microbiology 03 medical and health sciences 0302 clinical medicine Metronidazole medicine Animals Humans Amebicides Trophozoites Granulomatous amoebic encephalitis EC50 biology Chemistry 030108 mycology & parasitology biology.organism_classification medicine.disease Antimicrobial Infectious Diseases Acanthamoeba quina Acanthamoeba keratitis Insect Science Parasitology medicine.drug |
| Zdroj: | Acta Tropica. 216:105830 |
| ISSN: | 0001-706X |
| Popis: | Amoebae of the genus Acanthamoeba are worldwide distributed causative agents of serious human infections such as granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). To date, treatment of these infections is non-uniform and frequently unsuccessful. Recently, the phosphonium salts were studied for their high levels of antimicrobial activity. This work was aimed to investigate the cytotoxic effect of metronidazole and two phosphonium salts (PS1, PS2) on two clinical Acanthamoeba isolates. The isolates showed distinctly higher susceptibility to both phosphonium salts than to metronidazole. The highest susceptibility was noted to PS1 after 48 h of incubation. Metronidazole derivate PS2 showed higher susceptibility than metronidazole. The values of EC50 of PS2 were approximately twenty times lower than EC50 of metronidazole for Acanthamoeba lugdunensis strain and sixteen times lower for Acanthamoeba quina strain after 48 h. Although the therapeutic effect of metronidazole in Acanthamoeba infections is usually insufficient, its derivatisation can result in a significantly higher amoebicidal effect. Cytomorphological changes of trophozoites after exposure to tested compounds included rounding up of the cells, damage of membrane integrity, presence of pathological protrusions, elongation of the cells or pseudocyst-like stages. Obtained results indicate possible therapeutic potential of studied phosphonium salts. |
| Databáze: | OpenAIRE |
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