Effect of Antimicrobial Compounds on Balamuthia mandrillaris Encystment and Human Brain Microvascular Endothelial Cell Cytopathogenicity

Abstract

Cycloheximide, ketoconazole, or preexposure of organisms to cytochalasin D prevented Balamuthia mandrillaris-associated cytopathogenicity in human brain microvascular endothelial cells, which constitute the bloodbrain barrier. In an assay for inhibition of cyst production, these three agents prevented the production of cysts, suggesting that the biosynthesis of proteins and ergosterol and the polymerization of actin are important in cytopathogenicity and encystment.

The In Vitro Efficacy of Antimicrobial Agents Against the Pathogenic Free‐Living Amoeba Balamuthia mandrillaris

“…Similarly, we found pentamidine to have no amoebacidal activity even at the highest test concentration of 500 lM; although this compound has been reported as amoebastatic (inhibition of trophozoite replication) at 1 and 10 lg/ml (1.69 and 16.87 lM) in another study . Ketoconazole has been shown to prevent encystment in B. mandrillaris and inhibit mammalian cell line cytopathogenicity (Siddiqui et al 2007). In this study, we tested the related imidazole compound sulconazole and found no activity against the trophozoite or cyst stage.…”

“…Ketoconazole has been shown to prevent encystment in B. mandrillaris and inhibit mammalian cell line cytopathogenicity (Siddiqui et al. ). In this study, we tested the related imidazole compound sulconazole and found no activity against the trophozoite or cyst stage.…”

Balamuthia mandrillaris: Staining Properties of Cysts and Trophozoites and the Effect of 2,6‐Dichlorobenzonitrile and Calcofluor White on Encystment

“…Balamuthia mandrillaris (2 Â 10 5 amoebae/ml/well) were inoculated into 24-well plates containing RPMI-1640 (supplemented with 2 mM glutamine), and maintained at 37 1C for 48 h. Next, the total number of cells (cysts and trophozoites) was counted using a haemocytometer. Sodium dodecyl sulphate (SDS; 0.5% [w/v] final concentration) was added to lyse the trophozoites, and counts were performed again to determine the number of cysts, which are resistant to SDS detergent lysis (Siddiqui et al 2007). The percentage of encysting B. mandrillaris was determined as follows: number of SDS resistant cells/number of total amoebae (pre-SDS treatment) Â 100 5 % encystment.…”

Successful Treatment ofBalamuthia mandrillarisAmoebic Infection with Extensive Neurological and Cutaneous Involvement

“…Most of the available drugs are amebistatic: phenothiazine compounds, pentamidine isethionate, macrolides, azoles, TMP-SMX, and amphotericin B [7]. In addition, B. mandrillaris escapes the effect of antimicrobials by encysting in tissues, establishing chronic infections that may reactivate later [11]. Use of amebicidal drugs for treating this condition may not only kill trophozoites in active lesions, but may also prevent the further dissemination of the infection to the CNS and other organs, which has been invariably observed when amebistatic drugs are used.…”