Balamuthia mandrillaris

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Balamuthia mandrillaris observed under light, scanning and transmission electron microscope Image credit: Gonzalez-Robles, Science Direct.

Classification

Eukaryota; Amoebozoa; Discosea; longamoebia; Balamuthiidae

Species

NCBI: [1]

Balamuthia mandrillaris

Description and Significance

Balamuthia mandrillaris, a free-living amoeba, is the causative agent of the rare yet fatal neurological condition known as granulomatous amoebic encephalitis (GAE). Discovered in 1986 within the brain of a deceased mandrill at the San Diego Wild Animal Park. The pathogen was successfully isolated and studied for the first time in 1993 by Govinda Visvesvara, paying tribute to his mentor William Balamuth for his amoebae research. (Cope et al.,2019)

B. mandrillaris primarily dwells in soil and poses a great threat to human health. This amoeba can invade the human body through open wounds or inhalation, and it has been isolated from soil samples. Believed to be found across temperate regions globally, evidence supporting this includes the detection of antibodies to the protist in the bloodstream of healthy individuals (Schuster et al.,2003).A comprehensive understanding of the ecology and pathogenesis of B. mandrillaris is essential for effective prevention and treatment strategies against infections caused by this amoeba (Baig, 2015).

Genome Structure

The genome of Balamuthia mandrillaris is characterized by its complexity and unique features. B. mandrillaris possesses a relatively large genome with multiple chromosomes. The specific number of chromosomes is not mentioned but it may vary between different strains. The genome is circular, which is a common feature among amoebas. The draft genome highlights the importance of reference genome sequencing for this pathogen, emphasizing the ongoing efforts to assemble a comprehensive and accurate genomic sequence (Greninger et al., 2015).

Cell Structure, Metabolism and Life Cycle

The cell structure of B. mandrillaris is characterized by a distinctive amoeboid form with a central granular endoplasm and a clear ectoplasm, enabling motility and phagocytosis. B. mandrillaris exhibits a unique multilayered cell wall, a distinguishing feature among free-living amoebas, which likely contributes to its resilience and virulence in causing infections (Khan & Siddiqui 2015).

B. mandrillaris is a heterotrophic amoeba, relying on external food sources for energy. The organism gains energy through phagocytosis, actively ingesting bacteria and other particles. As part of its metabolic activity, B. mandrillaris produces molecules such as adenosine triphosphate (ATP), reflecting its capacity for cellular energy generation during the trophozoite stage (Feldman & Yohannan 2019).

The life cycle of Balamuthia mandrillaris involves a trophic amoeboid stage and a cystic stage, both of which are infectious. During the trophic stage it actively feeds on bacteria for metabolic purposes. The trophozoite is pleomorphic and uninucleated, but rarely can be binucleated. The crucial transition occurs when the amoeba transforms into a dormant cyst, enabling its survival in adverse conditions. During the cyst stage, B. mandrillaris produces a protective outer ectocyst layer, and the cysts serve as the main infectious form responsible for the transmission of the pathogen (Khan & Siddiqui 2015).

Ecology and Pathogenesis

B. mandrillaris has been associated with amebic encephalitis, highlighting its presence in soil and freshwater environments, specifically in moist and warm regions. While its symbiotic relationships and biogeochemical significance are not explicitly detailed, its contributions to the environment involve its role as a free-living organism in microbial communities (Schuster et al., 2003). Understanding the ecology of B. mandrillaris will help solve its interactions within the environment and impacts on human health, as one can contract it during an activity like swimming.

The pathogenicity of B. mandrillaris begins in granulomatous amoebic encephalitis (GAE), particularly affecting immunocompromised hosts (Bhosale & Parija, 2021). The organism's ability to cause disease in humans is marked by its neurotropic nature, leading to severe neurological symptoms. Virulence factors contributing to its pathogenesis remain areas of active research. (Baig, 2014). B. mandrillaris is bigger than the size of human leukocytes, rendering phagocytosis impossible. Instead, the immune system tries to confine the amoeba at the point of entry (open wound), by initiating a type IV hypersensitivity reaction (Baig, 2015) Upon infiltration, the amoeba may induce a skin lesion or migrate to the brain, causing GAE,(Cope et al., 2019) which is often fatal. This granulomatous characteristic is mainly seen in immunocompetent patients, while immunocompromised patients display "perivascular cuffing" (Baig, 2014). Balamuthia-induced GAE manifests with symptoms like focal paralysis, seizures, and brainstem manifestations (Bhosale & Parija, 2021).

Diagnostic Evaluation of Fatal Balamuthia mandrillaris Image credit: Hawkins, Primates.

References

Baig A (2014, December). Granulomatous amoebic encephalitis: ghost response of an immunocompromised host? J Med Microbiol, 63(12), 1763–1766. https://doi.org/10.1099/jmm.0.081315-0 PMID: 25239626

Baig AM (2015, April). Pathogenesis of amoebic encephalitis: Are the amoebas being credited to an 'inside job' done by the host immune response? Acta Tropica, 148, 72–76. https://doi.org/10.1016/j.actatropica.2015.04.022

Bhosale NK, Parija SC. (2021). Balamuthia mandrillaris: An opportunistic, free-living ameba – An updated review. Tropical Parasitology, 11(2), 78–88. https://doi.org/10.4103/tp.tp_36_21 PMID: 34765527

Cope JR, Landa J, Nethercut H, Collier SA, Glaser C, Moser M, Puttagunta R, Yoder JS, Ali IK, Roy SL (2019) The Epidemiology and Clinical Features of Balamuthia mandrillaris Disease in the United States, 1974–2016. Clinical Infectious Diseases 68(11): 1815–1822. https://doi.org/10.1093/cid/ciy813

Greninger AL, Messacar K, Dunnebacke T, Naccache SN, Federman S, Bouquet J, Mirsky D, Nomura Y, Yagi S, Glaser C, Vollmer M, Press CA, Kleinschmidt-DeMasters BK, Dominguez SR, Chiu CY (2015) Clinical metagenomic identification of Balamuthia mandrillaris encephalitis and assembly of the draft genome: the continuing case for reference genome sequencing. Genome Medicine 7(1): 113. https://doi.org/10.1186/s13073-015-0235-2

Schuster FL, Dunnebacke TH, Booton GC, Yagi S, Kohlmeier CK, Glaser C, Vugia D, Bakardjiev A, Azimi P, Maddux-Gonzalez M, Martinez AJ, Visvesvara GS (2003) Environmental Isolation of Balamuthia mandrillaris Associated with a Case of Amebic Encephalitis. J. Clin. Microbiol. 41(7): 3175–3180. https://doi.org/10.1128/JCM.41.7.3175-3180.2003

Siddiqui R, Khan NA (2015). "Balamuthia mandrillaris: Morphology, biology, and virulence". Trop. Parasitol. 5(1): 15–22. https://doi.org/10.4103/2229-5070.149888

Yohannan B, Feldman M (2019). Fatal Balamuthia mandrillaris encephalitis. Case Reports in Infectious Diseases 2019: 1–5. https://doi.org/10.1155/2019/9315756

Author

Page authored by Bella Readling, student of Prof. Bradley Tolar at UNC Wilmington.