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MBio Aug 2017ingests fragments of live host cells in a nibbling-like process termed amebic trogocytosis. Amebic trogocytosis is required for cell killing and contributes to tissue...
ingests fragments of live host cells in a nibbling-like process termed amebic trogocytosis. Amebic trogocytosis is required for cell killing and contributes to tissue invasion, which is a hallmark of invasive amebic colitis. Work done prior to the discovery of amebic trogocytosis showed that acid vesicles are required for amebic cytotoxicity. In the present study, we show that acidified lysosomes are required for amebic trogocytosis and cell killing. Interference with lysosome acidification using ammonium chloride, a weak base, or concanamycin A, a vacuolar H ATPase inhibitor, decreased amebic trogocytosis and amebic cytotoxicity. Our data suggest that the inhibitors do not impair the ingestion of an initial fragment but rather block continued trogocytosis and the ingestion of multiple fragments. The acidification inhibitors also decreased phagocytosis, but not fluid-phase endocytosis. These data suggest that amebic lysosomes play a crucial role in amebic trogocytosis, phagocytosis, and cell killing. is a protozoan parasite that is prevalent in low-income countries, where it causes potentially fatal diarrhea, dysentery, and liver abscesses. Tissue destruction is a hallmark of invasive infection. The parasite is highly cytotoxic to a wide range of human cells, and parasite cytotoxic activity is likely to drive tissue destruction. is able to kill human cells through amebic trogocytosis. This process also contributes to tissue invasion. Trogocytosis has been observed in other organisms; however, little is known about the mechanism in any system. We show that interference with lysosomal acidification impairs amebic trogocytosis, phagocytosis, and cell killing, indicating that amebic lysosomes are critically important for these processes.
Topics: Ammonium Chloride; Cell Survival; Endocytosis; Entamoeba histolytica; Host-Pathogen Interactions; Humans; Hydrogen-Ion Concentration; Jurkat Cells; Lysosomes; Macrolides; Phagocytosis; Pinocytosis
PubMed: 28851845
DOI: 10.1128/mBio.01187-17 -
Research in Microbiology 2011Entamoeba histolytica is a human pathogen that causes amoebic dysentery and leads to significant morbidity and mortality worldwide. Understanding the genome and... (Review)
Review
Entamoeba histolytica is a human pathogen that causes amoebic dysentery and leads to significant morbidity and mortality worldwide. Understanding the genome and evolution of the parasite will help explain how, when and why it causes disease. Here we review current knowledge about the evolutionary genomics of Entamoeba: how differences between the genomes of different species may help explain different phenotypes, and how variation among E. histolytica parasites reveals patterns of population structure. The imminent expansion of the amount genome data will greatly improve our knowledge of the genus and of pathogenic species within it.
Topics: Dysentery, Amebic; Entamoeba histolytica; Evolution, Molecular; Genome, Protozoan; Humans; Intestine, Large; Trophozoites
PubMed: 21288488
DOI: 10.1016/j.resmic.2011.01.007 -
Clinical Microbiology Reviews Oct 2003The detection of Entamoeba histolytica, the causative agent of amebiasis, is an important goal of the clinical microbiology laboratory. To assess the scope of E.... (Review)
Review
The detection of Entamoeba histolytica, the causative agent of amebiasis, is an important goal of the clinical microbiology laboratory. To assess the scope of E. histolytica infection, it is necessary to utilize accurate diagnostic tools. As more is discovered about the molecular and cell biology of E. histolytica, there is great potential for further understanding the pathogenesis of amebiasis. Molecular biology-based diagnosis may become the technique of choice in the future because establishment of these protozoa in culture is still not a routine clinical laboratory process. In all cases, combination of serologic tests with detection of the parasite (by antigen detection or PCR) offers the best approach to diagnosis, while PCR techniques remain impractical in many developing country settings. The detection of amebic markers in serum in patients with amebic colitis and liver abscess appears promising but is still only a research tool. On the other hand, stool antigen detection tests offer a practical, sensitive, and specific way for the clinical laboratory to detect intestinal E. histolytica. All the current tests suffer from the fact that the antigens detected are denatured by fixation of the stool specimen, limiting testing to fresh or frozen samples.
Topics: Animals; Clinical Laboratory Techniques; Entamoeba; Entamoeba histolytica; Entamoebiasis; Humans; Parasitology
PubMed: 14557296
DOI: 10.1128/CMR.16.4.713-729.2003 -
IDCases 2023infections, which can be asymptomatic, are endemic to developing countries; traveling to such countries is a risk factor for contracting these infections. A 65-year-old...
infections, which can be asymptomatic, are endemic to developing countries; traveling to such countries is a risk factor for contracting these infections. A 65-year-old Japanese man was hospitalized for coronavirus disease 2019 (COVID-19)-associated respiratory distress, and was treated with remdesivir, dexamethasone, and oxygen supplementation. Although his respiratory condition improved and the oxygen support was discontinued, he developed a fever, severe abdominal pain, and diarrhea on day 13 of hospitalization. Fifteen years ago, he was hospitalized for diarrhea of an unknown origin in Suzhou, China, and had a history of passing loose stools for 1 year. Contrast-enhanced abdominal and pelvic computed tomography revealed liver abscesses in both lobes and intestinal edema from the ascending colon to the descending colon. The abscesses were suspected to be amebic based on the characteristics of the drained abscess fluid. The patient was treated with cefotaxime and metronidazole, and his temperature declined and abdominal pain improved. A culture analysis of abscess fluid yielded negative findings; however, polymerase chain reaction analyses of abscess and stool samples were positive for We speculated that the patient was infected with while in China, and that the corticosteroid usage for COVID-19 had exacerbated the infection. Clinicians should be aware that corticosteroid treatments can lead to recurrent invasive amebiasis in asymptomatic amebic carriers.
PubMed: 36447935
DOI: 10.1016/j.idcr.2022.e01648 -
Assay and Drug Development Technologies 2015The concept of the hypothesis-driven or observational-based expansion of the therapeutic application of drugs is very seductive. This is due to a number of factors, such... (Review)
Review
The concept of the hypothesis-driven or observational-based expansion of the therapeutic application of drugs is very seductive. This is due to a number of factors, such as lower cost of development, higher probability of success, near-term clinical potential, patient and societal benefit, and also the ability to apply the approach to rare, orphan, and underresearched diseases. Another highly attractive aspect is that the "barrier to entry" is low, at least in comparison to a full drug discovery operation. The availability of high-performance computing, and databases of various forms have also enhanced the ability to pose reasonable and testable hypotheses for drug repurposing, rescue, and repositioning. In this article we discuss several factors that are currently underdeveloped, or could benefit from clearer definition in articles presenting such work. We propose a classification scheme-drug repositioning evidence level (DREL)-for all drug repositioning projects, according to the level of scientific evidence. DREL ranges from zero, which refers to predictions that lack any experimental support, to four, which refers to drugs approved for the new indication. We also present a set of simple concepts that can allow rapid and effective filtering of hypotheses, leading to a focus on those that are most likely to lead to practical safe applications of an existing drug. Some promising repurposing leads for malaria (DREL-1) and amoebic dysentery (DREL-2) are discussed.
Topics: Animals; Antimalarials; Computational Biology; Drug Approval; Drug Evaluation, Preclinical; Drug Repositioning; Drug Therapy; Dysentery, Amebic; Humans
PubMed: 26241209
DOI: 10.1089/adt.2015.29011.tiodrrr -
Medicine Feb 2024Amebic colitis has been less prevalent in recent times in China, and the similarity of its symptoms to those of inflammatory bowel disease (IBD) results in the... (Review)
Review
RATIONALE
Amebic colitis has been less prevalent in recent times in China, and the similarity of its symptoms to those of inflammatory bowel disease (IBD) results in the difficulty of early identification and diagnosis.
PATIENT CONCERNS
A 31-year-old male who exhibited intermittent diarrhea and hematochezia was highly suspected as IBD initially. Despite the partial relief of symptoms following the administration of mesalamine, the endoscopic ulcers remained largely unchanged.
DIAGNOSES
Two years after the onset of mesalamine therapy, amebic cysts were detected in stool microscopy and trophozoites were found on the surface of cecal ulcers. The patient was then diagnosed with amebic colitis.
INTERVENTIONS
After 2 rounds of standardized metronidazole treatment, amebic colitis remained refractory until diloxanide was administered.
OUTCOMES
The patient remained asymptomatic, and the mucosa of colon was normal during the annual follow-up.
LESSONS
Individuals newly diagnosed with IBD should undergo essential screening for amebiasis. And the use of steroids should be taken with caution, especially in cases where the effect of mesalamine is limited. For symptomatic intestinal amebiasis, even after the administration of tissue amebicides, the continued use of luminal amebicides is necessary to prevent recurrence.
Topics: Male; Humans; Adult; Dysentery, Amebic; Amebicides; Mesalamine; Ulcer; Diagnosis, Differential; Inflammatory Bowel Diseases
PubMed: 38335414
DOI: 10.1097/MD.0000000000037195 -
Frontiers in Cellular and Infection... 2020Amebiasis is a neglected tropical disease which is caused by the protozoan parasite . This disease is one of the leading causes of diarrhea globally, affecting largely... (Review)
Review
Amebiasis is a neglected tropical disease which is caused by the protozoan parasite . This disease is one of the leading causes of diarrhea globally, affecting largely impoverished residents in developing countries. Amebiasis also remains one of the top causes of gastrointestinal diseases in returning international travellers. Despite having many side effects, metronidazole remains the drug of choice as an amebicidal tissue-active agent. However, emergence of metronidazole resistance in pathogens having similar anaerobic metabolism and also in laboratory strains of has necessitated the identification and development of new drug targets and therapeutic strategies against the parasite. Recent research in the field of amebiasis has led to a better understanding of the parasite's metabolic and cellular pathways and hence has been useful in identifying new drug targets. On the other hand, new molecules effective against amebiasis have been mined by modifying available compounds, thereby increasing their potency and efficacy and also by repurposing existing approved drugs. This review aims at compiling and examining up to date information on promising drug targets and drug molecules for the treatment of amebiasis.
Topics: Amebiasis; Drug Development; Dysentery, Amebic; Entamoeba histolytica; Humans; Metronidazole
PubMed: 33718258
DOI: 10.3389/fcimb.2020.628257 -
The Cochrane Database of Systematic... Jan 2019Infection with the protozoan Entamoeba histolytica is common in low- and middle-income countries, and up to 100,000 people with severe disease die every year. Adequate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Infection with the protozoan Entamoeba histolytica is common in low- and middle-income countries, and up to 100,000 people with severe disease die every year. Adequate therapy for amoebic colitis is necessary to reduce illness, prevent development of complicated disease and extraintestinal spread, and decrease transmission.
OBJECTIVES
To evaluate antiamoebic drugs for treating amoebic colitis.
SEARCH METHODS
We searched the available literature up to 22 March 2018. We searched the Cochrane Infectious Diseases Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, mRCT, and conference proceedings. We contacted individual researchers, organizations, and pharmaceutical companies, and we checked reference lists.
SELECTION CRITERIA
Randomized controlled trials of antiamoebic drugs given alone or in combination, compared with placebo or another antiamoebic drug, for treating adults and children with a diagnosis of amoebic colitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility and methodological quality of trials and extracted and analysed the data. We calculated clinical and parasitological failure rates and rates of relapse and adverse events as risk ratios (RRs) with 95% confidence intervals (CIs), using a random-effects model. We determined statistical heterogeneity and explored possible sources of heterogeneity using subgroup analyses. We carried out sensitivity analysis by using trial quality to assess the robustness of reported results.
MAIN RESULTS
In total, 41 trials (4999 participants) met the inclusion criteria of this review. In this update, we added four trials to the 37 trials included in the first published review version. Thirty trials were published over 20 years ago. Only one trial used adequate methods of randomization and allocation concealment, was blinded, and analysed all randomized participants. Only one trial used an E histolytica stool antigen test, and two trials used amoebic culture.Tinidazole may be more effective than metronidazole for reducing clinical failure (RR 0.28, 95% CI 0.15 to 0.51; 477 participants, eight trials; low-certainty evidence) and is probably associated with fewer adverse events (RR 0.65, 95% CI 0.46 to 0.92; 477 participants, 8 trials; moderate-certainty evidence). Compared with metronidazole, combination therapy may result in fewer parasitological failures (RR 0.36, 95% CI 0.15 to 0.86; 720 participants, 3 trials; low-certainty evidence), but we are uncertain which combination is more effective than another. Evidence is insufficient to allow conclusions regarding the efficacy of other antiamoebic drugs.
AUTHORS' CONCLUSIONS
Compared with metronidazole, tinidazole may be more effective in reducing clinical failure and may be associated with fewer adverse events. Combination drug therapy may be more effective for reducing parasitological failure compared with metronidazole alone. However, these results are based mostly on small trials conducted over 20 years ago with a variety of poorly defined outcomes. Tests that detect E histolytica more accurately are needed, particularly in countries where concomitant infection with other bacteria and parasites is common.
Topics: Amebicides; Animals; Drug Therapy, Combination; Dysentery, Amebic; Entamoeba histolytica; Humans; Metronidazole; Randomized Controlled Trials as Topic; Tinidazole
PubMed: 30624763
DOI: 10.1002/14651858.CD006085.pub3 -
Gut Feb 1973
Review
Topics: Animals; Anthelmintics; Antimony; Chloroquine; Coccidiosis; Diphyllobothriasis; Dysentery, Amebic; Emetine; Giardiasis; Humans; Infant; Intestinal Diseases, Parasitic; Liver Abscess, Amebic; Male; Metronidazole; Nematode Infections; Niclosamide; Niridazole; Schistosomiasis; Thiabendazole
PubMed: 4572292
DOI: 10.1136/gut.14.2.145 -
Parasitology International Sep 2011Entamoeba histolytica, a protozoan parasite, is an important cause of diarrhea and colitis in the developing world. Amebic colitis is characterized by ulceration of the...
Entamoeba histolytica, a protozoan parasite, is an important cause of diarrhea and colitis in the developing world. Amebic colitis is characterized by ulceration of the intestinal mucosa. We performed microarray analysis of intestinal biopsies during acute and convalescent amebiasis in order to identify genes potentially involved in tissue injury or repair. Colonic biopsy samples were obtained from 8 patients during acute E. histolytica colitis and again 60 days after recovery. Gene expression in the biopsies was evaluated using microarray, and confirmed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). REG 1A and REG 1B were the most up-regulated of all genes in the human intestine in acute versus convalescent E. histolytica disease: as determined by microarray, the levels of induction were 7.4-fold and 10.7 fold for REG 1A and B; p=0.003 and p=0.006 respectively. Increased expression of REG 1A and REG 1B protein in the colonic crypt epithelial cells during acute amebiasis was similarly observed by immunohistochemistry. Because REG 1 protein is anti-apoptotic and pro-proliferative, and since E. histolytica induces apoptosis of the intestinal epithelium as part of its disease process, we next tested if REG 1 might be protective during amebiasis by preventing parasite-induced apoptosis. Intestinal epithelial cells from REG 1-/- mice were found to be more susceptible to spontaneous, and parasite-induced, apoptosis in vitro (p=0.03). We concluded that REG 1A and REG 1B were upregulated during amebiasis and may function to protect the intestinal epithelium from parasite-induced apoptosis.
Topics: Adolescent; Adult; Animals; Apoptosis; Colon; Dysentery, Amebic; Entamoeba histolytica; Entamoebiasis; Epithelial Cells; Gene Expression; Gene Knockout Techniques; Humans; Intestines; Lithostathine; Mice; Mice, Inbred ICR; Mice, Knockout; Oligonucleotide Array Sequence Analysis; RNA; Young Adult
PubMed: 21586335
DOI: 10.1016/j.parint.2011.04.005