Entamoeba histolytica: Five facts about modeling a complex human disease in rodents

Cavazos, Carolina Mendoza; Knoll, Laura J.

doi:10.1371/journal.ppat.1008950

Cited by 9 publications

(7 citation statements)

References 48 publications

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“…(A) Cysts were scored from 0 to 3, where 0 represented an intact cyst and 3 is an empty chitin shell. Chitin (Calcofluor White), Jacob2 (1A4 antibody (17)), and nuclei (Syto11). Scale bar represents 10 μm.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, modeling the critical developmental stage interconversion that E. histolytica undergoes between ingestion and colonization of the cecum is not yet possible (16). A model that includes the developmental changes of excystation and encystation would allow the field to understand the transmission of the pathogen and find targets for intervention (reviewed in (17)), as only viable parasites completely encysted and shed via the fecal-oral route can contaminate food and water and infect a new host.…”

Section: Introductionmentioning

confidence: 99%

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Recapitulating the life cycle of the global pathogenEntamoebain mice

Cavazos

Heredia

Owens

et al. 2022

Preprint

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There are several Entamoeba species that colonize humans, but only Entamoeba histolytica causes severe disease. E. histolytica is transmitted through the fecal-oral route to colonize the intestinal tract of 50 million people worldwide. The current mouse model to study E. histolytica intestinal infection directly delivers the parasite into the surgically exposed cecum, which circumvents the natural route of infection and does not produce infectious cysts. To develop a fecal-oral mouse model, we screened our vivarium for a natural murine Entamoeba colonizer via a pan-Entamoeba PCR targeting the 18S ribosomal gene. We determined that C57BL/6 mice were chronically colonized by Entamoeba muris. This amoeba is closely related to E. histolytica, as determined by 18S sequencing and cross-reactivity with an E. histolytica-specific antibody. In contrast, outbred Swiss Webster (SW) mice were not chronically colonized by E. muris. We orally challenged SW mice with 1x105E. muris cysts and discovered they were susceptible to infection, with peak cyst shedding occurring between 5-7 days post-infection. Most infected SW mice did not lose weight significantly but trended toward decreased weight gain throughout the experiment when compared to mock-infected controls. Infected mice treated with paromomycin, an antibiotic used against non-invasive intestinal disease, do not become colonized by E. muris. Within the intestinal tract, E. muris localizes exclusively to the cecum and colon. Purified E. muris cysts treated with bovine bile in vitro excyst into mobile, pre-trophozoite stages. Overall, this work describes a novel fecal-oral mouse model for the important global pathogen E. histolytica.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recapitulating the life cycle of the global pathogenEntamoebain mice

Cavazos

Heredia

Owens

et al. 2022

Preprint

Self Cite

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show abstract

“…E. histolytica exhibits two forms during its life span; cyst which is resistant and infective and trophozoites which are motile and invasive. On the contrary, there is an unavailability of animal models that can show inter-conversion between the two forms and on the other, this inter-conversion is mandatory for disease propagation and pathogenesis (Cavazos & Knoll, 2020). A rodent model that is capable of producing E. histolytica cysts could serve this purpose and it could be a potent source in generating new treatment and vaccines for amoebiasis by targeting parasite development.…”

Section: Perspectivementioning

confidence: 99%

The flip side of reactive oxygen species in the tropical disease‐Amoebiasis

et al. 2021

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Entamoeba histolytica is the conductive agent of amoebiasis. Upon the parasite's infection, macrophages and neutrophils are activated by interferon γ, IL-13 and tumour necrosis factor. These immune cells then carry out the amoebicidal activity by releasing nitric oxide synthase and reactive oxygen species (ROS). This review talks about the protective and destructive role of ROS in Eh. E. histolytica has defence strategies against oxidative stress which is a result of excess ROS production. They possess antioxidants for their defence such as L-Cysteine, flavodiiron proteins, peroxiredoxin and trichostatin A, which contribute to the parasite's virulence. The ROS are harmful to the host cells as excess ROS production stimulates cell death by mechanisms like apoptosis and necroptosis. NADPH oxidase (NOX) is a key source of ROS in mammalian cells and causes apoptosis of host cells via the protein kinase transduction pathway. This review provides insights into why NOX inhibitors that could be a potent antiparasitic drug, is not effective for in vivo purposes. This paper also gives an insight into a solution that could be a potent source in generating new treatment and vaccines for amoebiasis by targeting parasite development.

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“…As many intestinal protists, such as Entamoeba spp., Endolimax nana , and Iodamoeba butschlii , are amoeba that can phagocytize bacteria, it follows logically that colonization with them will change the composition of the bacteriome. The most studied is the global pathogen Entamoeba histolytica , for which the bacteriome can provide nutrition after phagocytosis as well as serve as an immune response trainer, a first line of defense against colonization, or processor of metabolites that can be available as nutrition or inhibit parasite encystation [ 36 ]. The positive and negative effects of nonpathogenic amoeba interactions with bacteria have not yet been examined.…”

Section: Parasites and The Microbiomementioning

confidence: 99%