Balamuthia mandrillaris: role of galactose in encystment and identification of potential inhibitory targets

TitleBalamuthia mandrillaris: role of galactose in encystment and identification of potential inhibitory targets
Publication TypeJournal Article
Year of Publication2010
AuthorsSiddiqui R, Jarroll EL, Khan NA
JournalExp Parasitol
Volume126
Issue1
Pagination22 - 7
Date PublishedSep
ISSN1090-2449 (Electronic) 0014-4894 (Linking)
Accession Number19766634
KeywordsAmides / pharmacology, Amoebozoa / drug effects / *physiology, Brain / blood supply / cytology, Calcium-Binding Proteins / *physiology, Cells, Cultured, Chromones / pharmacology, Cytochalasin D / pharmacology, Cytoskeleton / drug effects / physiology, Endothelial Cells / parasitology, Enzyme Inhibitors / *pharmacology, Galactose / metabolism / *pharmacology, Genistein / pharmacology, Humans, Monosaccharide Transport Proteins / *physiology, Morpholines / pharmacology, Periplasmic Binding Proteins / *physiology, Phosphatidylinositol 3-Kinases / antagonists & inhibitors / metabolism, Protein Kinase Inhibitors / pharmacology, Protein Tyrosine Phosphatases / antagonists & inhibitors, Protein-Tyrosine Kinases / antagonists & inhibitors / metabolism, Pyridines / pharmacology, rho-Associated Kinases / antagonists & inhibitors, Signal Transduction / drug effects / physiology, Vanadates / pharmacology
Abstract

Balamuthia mandrillaris is a causative agent of granulomatous encephalitis that almost always proves fatal. A major concern during the course of therapy is that B. mandrillaris can transform into cysts. Cysts are highly resistant to physical and chemical conditions and present a problem in successful antimicrobial chemotherapy. However, the underlying mechanisms of B. mandrillaris transformation into cysts are not known. In this study, we examined the effects of exogenous sugars on B. mandrillaris encystment. The findings revealed that free exogenous galactose, but not other sugars, enhanced parasite differentiation into cysts, and apparently a galactose-binding protein is involved in B. mandrillaris encystment. Cytoskeletal re-arrangements and phosphatidylinositol 3-kinase (PI3K)-mediated pathways are involved in B. mandrillaris encystment based on inhibitor studies. Dual functionality of galactose-binding protein in B. mandrillaris pathogenesis and encystment is discussed further.

DOI10.1016/j.exppara.2009.09.013
Short TitleBalamuthia mandrillaris: role of galactose in encystment and identification of potential inhibitory targets
Notify Library Reference ID1406

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