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J Med Microbiol 56 (2007), 30-35; DOI: 10.1099/jmm.0.46847-0
© 2007 Society for General Microbiology
ISSN 1473-5644

Effects of human serum on Balamuthia mandrillaris interactions with human brain microvascular endothelial cells

Abdul Matin1, Seok Ryoul Jeong1, Monique Stins2 and Naveed Ahmed Khan1

1 School of Biological and Chemical Sciences, Birkbeck College, University of London, London WC1E 7HX, UK

2 Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Correspondence
Noveed Ahmed Khan
n.khan{at}sbc.bbk.ac.uk

Received 20 July 2006
Accepted 11 September 2006

Balamuthia mandrillaris is a free-living amoeba and a causative agent of fatal granulomatous encephalitis. In the transmission of B. mandrillaris into the central nervous system (CNS), haematogenous spread is thought to be the primary step, followed by blood–brain barrier penetration. The objectives of the present study were (i) to determine the effects of serum from healthy individuals on the viability of B. mandrillaris, and (ii) to determine the effects of serum on B. mandrillaris-mediated blood–brain barrier perturbations. It was determined that normal human serum exhibited limited amoebicidal effects, i.e. ~40 % of trophozoites were killed. The residual subpopulation, although viable, remained static over longer incubations. Using human brain microvascular endothelial cells (HBMEC), which form the blood–brain barrier, it was observed that B. mandrillaris exhibited binding (>80 %) and cytotoxicity (>70 %) to HBMEC. However, normal human serum exhibited more than 60 % inhibition of B. mandrillaris binding and cytotoxicity to HBMEC. ELISAs showed that both serum and saliva samples exhibit the presence of anti-B. mandrillaris antibodies. Western blots revealed that normal human serum reacted with several B. mandrillaris antigens with approximate molecular masses of 148, 115, 82, 67, 60, 56, 44, 42, 40 and 37 kDa. Overall, the results demonstrated that normal human serum has inhibitory effects on B. mandrillaris growth and viability, as well as on their binding and subsequent cytotoxicity to HBMEC. A complete understanding of B. mandrillaris pathogenesis is crucial to develop therapeutic interventions and/or to design preventative measures.

Abbreviations: BGE, Balamuthia granulomatous encephalitis; CNS, central nervous system; HBMEC, human brain microvascular endothelial cells; LDH, lactate dehydrogenase; sIgA, secretory IgA.




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