Cytopathogenicity of Balamuthia mandrillaris, an Opportunistic Causative Agent of Granulomatous Amebic Encephalitis

Abstract

Balamuthia mandrillaris is a free-living ameba and an opportunistic agent of lethal granulomatous amebic encephalitis in humans and other mammals. Balamuthia mandrillaris is highly cytopathic but, in contrast to the related Acanthamoeba, does not feed on bacteria and seems to feed only on eukaryotic cells instead. Most likely, the cytopathogenicity of B. mandrillaris is inseparable from its infectivity and pathogenicity. To better understand the mechanisms of B. mandrillaris cytopathogenicity, an assay for measuring amebic cytolytic activity was adapted that is based on the release of a reporter enzyme by damaged target cells. The ameba is shown to lyse murine mastocytoma cells very efficiently in a time- and dose-related manner. Furthermore, experiments involving semipermeable membranes and phagocytosis inhibitors indicate that the cytolytic activity of B. mandrillaris is essentially cell contact-dependent. Standard and fluorescence light microscopy, as well as scanning and transmission electron microscopy support and extend these findings at the ultrastructural level.

Balamuthia mandrillaris, an opportunistic agent of granulomatous amebic encephalitis, infects the brain via the olfactory nerve pathway

“…How the amebae pass the basement membrane is not known and cannot be concluded from these micrographs. However, B. mandrillaris are highly cytolytic in vitro (Kiderlen et al 2000) and possess phospholipase, lysophospholipase and neutral lipase activities (Shadrach et al 2004), which might be involved in this step. Nevertheless, the basement membrane was traversed without obvious tissue destruction and very large, elongated amebae were found in the submucosal nerve plexus or lamina propria.…”

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

“…As shown in Table 2, cytochalasin D partially inhibited B. mandrillaris-mediated HBMEC death, suggesting that B. mandrillaris uses phagocytic processes to produce HBMEC damage. Because host cell destruction is a result of contact (8,10), the term cytopathogenicity is used. In support, parasite-conditioned medium did not produce HBMEC destruction.…”

Oral infection of immunocompetent and immunodeficient mice with Balamuthia mandrillaris amebae

“…Should B. mandrillaris definitely not survive in fecal matter, this would point to the stomach or duodenum as likely areas. The known cyto-and histopathic potential of B. mandrillaris trophozoites (Visvesvara et al 1993;Kiderlen et al 2006) and repeated findings of amebae buried deeply in the gut wall (Fig. 4d) and of tissue damage in the small intestine (Fig.…”

“…The amebae were then adapted to axenic culture in BM-3 medium and Chang Special Medium (Kiderlen et al 2006) and kept at 37°C in humidified normal atmosphere with 6% CO 2 . Every 3-6 months, the amebae were passaged in mice by nasal instillation and reisolated from brain tissue.…”