World Journal of Microbiology and Biotechnology

, Volume 30, Issue 9, pp 2337–2342

Laboratory testing of clinically approved drugs against Balamuthia mandrillaris

Authors

  • Huma Kalsoom
    • Department of Biological and Biomedical SciencesAga Khan University
  • Abdul Mannan Baig
    • Department of Biological and Biomedical SciencesAga Khan University
    • Department of Biological and Biomedical SciencesAga Khan University
  • Ruqaiyyah Siddiqui
    • Department of Biological and Biomedical SciencesAga Khan University
Original Paper

DOI: 10.1007/s11274-014-1658-4

Cite this article as:
Kalsoom, H., Baig, A.M., Khan, N.A. et al. World J Microbiol Biotechnol (2014) 30: 2337. doi:10.1007/s11274-014-1658-4

Abstract

Balamuthia mandrillaris is a free-living protist pathogen that can cause life-threatening granulomatous amoebic encephalitis. Given the lack of effective available drugs against B. mandrillaris encephalitis with a mortality rate of more than 90 %, here we screened drugs, targeting vital cellular receptors and biochemical pathways, that are already in approved clinical use for their potential clinical usefulness. Amoebicidal assays were performed by incubating B. mandrillaris with drugs (3 × 105 cells/0.5 mL/well) in phosphate buffered saline for 24 h and viability was determined using Trypan blue exclusion staining. For controls, amoebae were incubated with the solvent alone. To determine whether effects are reversible, B. mandrillaris were pre-exposed to drugs for 24 h, washed twice, and incubated with human brain microvascular endothelial cells, which constitute the blood–brain barrier as food source, for up to 48 h. Of the ten drugs tested, amlodipine, apomorphine, demethoxycurcumin, haloperidol, loperamide, prochlorperazine, procyclidine, and resveratrol showed potent amoebicidal effects, while amiodarone and digoxin exhibited minimal effectiveness. When pre-treated with these drugs, no viable trophozoites re-emerged, suggesting that drugs destroyed parasite irreversibly. Based on the in vitro assay, amlodipine, apomorphine, demethoxycurcumin, haloperidol, loperamide, prochlorperazine, procyclidine, and resveratrol are potential antimicrobials for further testing against B. mandrillaris encephalitis. These findings may provide novel strategies for therapy but further research is needed to determine clinical usefulness of aforementioned drugs against granulomatous amoebic encephalitis caused by B. mandrillaris, and other free-living amoebae, such as Acanthamoeba spp., and Naegleria fowleri.

Keywords

Balamuthia mandrillaris Clinical drugs In vitro Amoebicidal Encephalitis

Copyright information

© Springer Science+Business Media Dordrecht 2014