Significance of amebiasis: 10 reasons why neglecting amebiasis might come back to bite us in the gut

Shirley, Debbie-Ann; Watanabe, Kôji; Moonah, Shannon

doi:10.1371/journal.pntd.0007744

Cited by 49 publications

(52 citation statements)

References 53 publications

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“…That said, new therapies are urgently needed given the lack of effective vaccines, drug resistance, limited efficacy and toxicity associated with current treatment (2)(3)(4). Given that the UPS pathway is essential for cell survival, inhibition of the proteasome has emerged as an attractive anti-parasitic target (5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

COP9 signalosome is an essential and druggable parasite target that regulates protein degradation

Ghosh

Farr

Singh

et al. 2020

Preprint

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Understanding how the protozoan protein degradation pathway is regulated could uncover new parasite biology for drug discovery. We found the COP9 signalosome (CSN) conserved in multiple pathogens such as Leishmania, Trypanosoma, Toxoplasma, and used the severe diarrhea-causing Entamoeba histolytica to study its function in medically significant protozoa. We show that CSN is an essential upstream regulator of parasite protein degradation. Genetic disruption of E. histolytica CSN by two distinct approaches inhibited cell proliferation and viability. Both CSN5 knockdown and dominant negative mutation trapped cullin in a neddylated state, disrupting UPS activity and protein degradation. In addition, zinc ditiocarb (ZnDTC), a main metabolite of the inexpensive FDA-approved alcohol-abuse drug disulfiram, was active against parasites acting in a COP9-dependent manner. ZnDTC, given as disulfiram-zinc, had oral efficacy in clearing parasites in vivo. Our findings provide insights into the regulation of parasite protein degradation, and supports the significant therapeutic potential of COP9 inhibition.Summary sentenceParasite-encoded COP9 signalosome is an essential upstream regulator of ubiquitin-proteasome mediated protein degradation, and shows significant potential as a therapeutic target.

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Section: Introductionmentioning

confidence: 99%

COP9 signalosome is an essential and druggable parasite target that regulates protein degradation

Ghosh

Farr

Singh

et al. 2020

Preprint

Self Cite

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show abstract

“…This case of invasive amoebiasis in early pregnancy outside of endemic regions and several years after exposure demonstrates the importance of broad differential diagnostics in the workup of a liver abscess including thorough investigation of the patient’s travel history. Amoebiasis represents a common travel-associated parasitic gastrointestinal infection in western Europe and north America, however, it remains an underestimated disease [ 5 , 43 ]. Management of the less frequent invasive form of amoebiasis in such a unique clinical setting like pregnancy is a complex task.…”

Section: Limitationsmentioning

confidence: 99%

Development of amoebic liver abscess in early pregnancy years after initial amoebic exposure: a case report

et al. 2020

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Background Infection with Entamoeba histolytica and associated complications are relatively rare in developed countries. The overall low prevalence in the Western world as well as the possibly prolonged latency period between infection with the causing pathogen and onset of clinical symptoms may delay diagnosis of and adequate treatment for amoebiasis. Amoebic liver abscess (ALA) is the most common extraintestinal manifestation of invasive amoebiasis. Pregnancy has been described as a risk factor for development of invasive amoebiasis and management of these patients is especially complex. Case presentation A 30-year-old Caucasian woman in early pregnancy presented to our emergency department with abdominal pain alongside elevated inflammatory markers and liver function tests. Travel history revealed multiple journeys to tropic and subtropic regions during the past decade and a prolonged episode of intermittently bloody diarrhea during a five month stay in Indonesia seven years prior to admission. Sonographic and magnetic resonance imaging revealed a 5 × 4 cm hepatic abscess. After ultrasound-guided transcutaneous liver drainage, both abscess fluids and blood cultures showed neither bacterial growth nor microscopic signs of parasitic disease. Serological testing confirmed an infection with Entamoeba histolytica, which was treated with metronidazole, followed by eradication therapy with paromomycin. Subsequent clinical, laboratory and imaging follow-up exams showed regression of the ALA. In addition, the pregnancy completed without complications and a healthy baby boy was born 7 months after termination of treatment. Conclusions This case of invasive amoebiasis in early pregnancy outside of endemic regions and several years after exposure demonstrates the importance of broad differential diagnostics in the context of liver abscesses. The complex interdisciplinary decisions regarding the choice of imaging techniques as well as interventional and antibiotic therapy in the context of pregnancy are discussed. Furthermore, we present possible explanations for pregnancy as a risk factor for an invasive course of amoebiasis.

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“…Globally, an average of 50 million cases and 55,000 to 100,000 deaths are due to E. histolytica infection each year, primarily impacting the developing world [1,2]. The world is widely unprepared for an outbreak of E. histolytica due to the lack of a vaccine and the use of a single drug type as treatment (reviewed in [3]). E. histolytica is the causative agent of the diarrheal disease known as amebiasis, but it can sometimes penetrate the intestinal wall, enter the circulation, and cause abscesses throughout the body, most commonly in the liver.…”

Section: Fact 1: Rodent Models Do Not Mimic the Entire Life Cycle Of mentioning

confidence: 99%

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

Cavazos¹,

Knoll²

2020

PLoS Pathog

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Significance of amebiasis: 10 reasons why neglecting amebiasis might come back to bite us in the gut

Cited by 49 publications

References 53 publications

COP9 signalosome is an essential and druggable parasite target that regulates protein degradation

COP9 signalosome is an essential and druggable parasite target that regulates protein degradation

Development of amoebic liver abscess in early pregnancy years after initial amoebic exposure: a case report

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

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