Pathogenesis of amebiasis

doi:10.1016/S1369-5274(02)00335-1

Current Opinion in Microbiology

Volume 5, Issue 4, 1 August 2002, Pages 443-447

https://doi.org/10.1016/S1369-5274(02)00335-1 Get rights and content

Abstract

It is an exciting time in the study of Entamoeba histolytica. Over the past two years, the natural history and burden of disease in humans has been redefined, mucosal immune responses associated with protection identified, and the developmental regulation of encystation outlined. The number of genes sequenced has increased from a few hundred to a few thousand, and study of the genome structure is revealing unusual repetitive elements and plasticity. DNA microarrays promise the first ability to examine global patterns of mRNA abundance. The mechanism of transcriptional control via histone modifications and sequence-specific DNA-binding proteins are to be delineated. Advances in cell biology are providing new insights into invasion through the intestinal epithelium.

Section snippets

Introduction: amebiasis in humans

The availability of accurate diagnostic tests for Entamoeba histolytica infection has enabled a fresh look at the epidemiology and natural history of amebiasis 1•., 2., 3., 4••., 5., 6., 7., 8., 9., 10., 11•.. Haque and colleagues are examining the natural history of amebiasis in pre-school children from an urban slum of Dhaka. New E. histolytica infections were detected in half of the children during two years of observation [4••]. Of children with asymptomatic E. histolytica infection, one in

Determinants of parasite invasiveness

Inroads are being made on the contributions of environmental factors such as intestinal flora or malnutrition that affect disease progression in amebiasis. Mirelman's group 12., 13. has shown that Escherichia coli serotype 055 is phagocytosed via the parasite Gal/GalNAc lectin. Uptake of the bacteria and long-term (day-long) culture of the bacteria with the parasite results in an 80–90% decrease in adherence, cytotoxicity and capability of the parasite to form hamster liver abscess. After

The amoebapore and cytotoxicity

Leippe's laboratory has pioneered investigation of the amoebapore gene family 16., 17•., 18.. Amoebapore proteins migrate as 5 kDa molecules on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and are 77 amino acids long with six cysteines. There are three amoebapore proteins (A, B and C): A and B have 57% identity; A and C have 47% identity; and B and C have 35% identity. The proteins appear to form pores in cell membranes by a barrel-stave mechanism similar to that of

Interaction with intestinal epithelium

Leroy [19] is studying the initial steps in the interaction of E. histolytica with polarized intestinal epithelial cells. Invasion through the intestinal epithelium initiates disease. Leroy has previously shown that the amebae disturb the enterocyte epithelial tight junctions early in the interaction. Sonicates of the amebae had no effect. Inhibition of the Gal/GalNAc lectin blocked tight junction disruption, demonstrating the requirement for contact of the intact parasite with the epithelium.

RAB proteins

Between 40 and 45 Rab GTPases in E. histolytica regulate vesicular trafficking 23., 24., 25.. Nozaki and colleagues [23] are concentrating on Rab5 and Rab7 and deciphering their role in regulation of vesicular fusion in the endocytic/phagocytic pathway. The role of these proteins in E. histolytica appears to be quite different from that in metazoan cells. In resting cells, Rab5 and Rab7 are not in the same location in the cell, but are individually localized to small vesicles. Within five

Genomics

Progress is rapid in the understanding of the genome structure of E. histolytica 26., 27., 28., 29., 30., 31.. At metaphase, 30–50 chromosomes can be resolved, and with pulsed-field gel electrophoresis (PFGE), one can separate the chromosomes of the parasite, although they are not as distinct as the chromosome bands of yeast similarly separated by PFGE. There is plasticity in the size of chromosomes between isolates of E. histolytica. Hybridization of cDNAs to PFGE by Tannich's laboratory 26.,

Transcription regulation

The first sequence-specific transcription factors binding to upstream regulatory elements of E. histolytica protein-encoding gene promoters were identified in 2001 32••., 33.. The proteins that recognize upstream regulatory element (URE) 4 in the lectin hgl5 promoter contain RNA recognition motifs, whereas the URE3-binding protein lacks a classical DNA-binding domain but contains two EF-hand calcium-binding motifs. Gilchrist [32••] has discovered that calcium controls the in vitro ability of

Encystation and excystation

An area that has seen profound advances in understanding is the regulation of the developmental change of trophozoite to cyst. Encystment of the reptilian parasite Entamoeba invadens is being studied in Eichinger's laboratory 34••., 35., 36.. Upon placement in encystment media, E. invadens trophozoites aggregate within two hours. It is from these aggregates that cysts develop within 22 hours. Eichinger has discovered that galactose blocks, and galactose terminal proteins such as mucin

Conclusions

One in 10 children in Bangladesh dies before his or her fifth birthday. One third of these deaths are due to diarrheal diseases such as amebiasis. It is heartening to see the application of molecular biology to the problem of amebic colitis. The joint efforts of scientists from the developing and developed worlds reviewed here promise to provide solutions for one of the great neglected diseases of mankind.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

• of special interest
•• of outstanding interest

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2020, Molecular Advancements in Tropical Diseases Drug Discovery
Amebiasis is caused by Entamoeba histolytica that remains a global health burden mainly in developing countries despite advancements in neglected tropical disease control programs by WHO. Patients with symptomatic amebiasis commonly present with amebic colitis and amebic liver abscess though most infected individuals are asymptomatic. The latter is the reservoir of this protozoan parasite and eventually causes the disease transmission. Therefore the new strategy in developing drugs and vaccines that can block disease transmission is important because only a few drugs are available in the market and the absence of effective vaccines to combat amebiasis. To accomplish that, a new diagnostic tool that can differentiate E. histolytica infection stages and nonpathogenic Entamoeba would be highly recommended.
Entamoeba Histolytica: Biology and host immunity
2019, Encyclopedia of Microbiology
Entamoeba histolytica is an intestinal dwelling parasite in the human gastrointestinal tract that causes diseases such as amebiasis, amebic colitis and amebic liver abscesses. In most cases, E. histolytica colonizes the host's gut without causing symptoms or disease. However, for unknown reasons, in 10% of people with E. histolytica becomes pathogenic and causes amebiasis and in some cases extraintestinal diseases. Diagnostic tools have become readily available to accurately identifying E. histolytica infection, and well-accepted medications have been discovered to treat patients who have amebiasis or a related disease. Much of E. histolytica’s success as a pathogen is owed to the well adapted virulence factors that are able to colonize the host, degrade host innate defenses and subvert host immune response in order to invade the host. However, the human immune system is also well adapted in reducing E. histolytica infection. As researchers continue to investigate E. histolytica, more light will be shed on the interaction between parasite and host, and better treatment options may become available for patients use.
Inflammatory Enteritis
2017, Principles and Practice of Pediatric Infectious Diseases
Entamoeba histolytica
2013, Microbiology of Waterborne Diseases: Microbiological Aspects and Risks: Second Edition
This chapter discusses Entamoeba histolytica, basic microbiology, natural history and life cycle, clinical features, pathogenicity, virulence and causation, treatment, methods of detection, survival and detection in the environment and in water, a critical review of the epidemiology and, finally, risk assessment. Differentiation between pathogenic E. histolytica and non-pathogenic species is fundamental to the epidemiology and control of infection. The reuse of human wastewater has been identified as an important source of human infection. Infection can be asymptomatic or cause relatively mild intestinal upset and diarrhoea, or more severe amoebiasis in the form of amoebic characterized by stomach pain, bloody stools and fever. Rarely, E. histolytica can invade other parts of the body such as the liver, lungs, or brain. Infected people shed cysts in their faeces, which are then transmitted by the ingestion of faecally-contaminated food, water, or from person-to-person contact. Waterborne transmission is commonly associated with faecally-contaminated water supplies in developing countries. The cysts are relatively resistant to disinfection and may not be inactivated by chlorination practices generally applied in drinking water treatment but are inactivated by hyperchlorination, iodination and UV.
Common pathways for receptor-mediated ingestion of Escherichia coli and LDL cholesterol by Entamoeba histolytica regulated in part by transmembrane kinase 39
2012, International Journal for Parasitology
Citation Excerpt :
Host cell death is primarily mediated via an amoeba-induced rapid activation of caspase-3 dependent apoptosis (Huston et al., 2000, 2003). Trophozoites encyst in the intestine due to unknown stimuli and are passed in the stool (Petri, 2002). Trophozoites are phagocytic in the intestine and ingest a wide variety of targets.
The single-celled parasite, Entamoeba histolytica, is an enteric pathogen that ingests bacteria and host cells. Inhibition of phagocytosis renders the parasite avirulent. The ligand/receptor interactions that allow E. histolytica to phagocytose are not well understood. We hypothesised that E. histolytica trophozoites might accomplish ingestion through the utilisation of a scavenger receptor for cholesterol. Here we show that acetylated low density lipoprotein cholesterol was phagocytosed by amoebae via receptor-mediated mechanisms. Acetylated low density lipoprotein cholesterol competitively inhibited by 31 ± 1.3% (P < 0.005) the ingestion of Escherichia coli, but not erythrocytes and Jurkat T lymphocytes, suggesting a partially redundant phagocytic pathway for E. coli and cholesterol. Inducible expression of a signalling-dead dominant-negative version of E. histolytica transmembrane kinase 39 inhibited ingestion of E. coli by 55 ± 3% (P < 0.005) but not LDL particles. We concluded that ingestion of E. coli was regulated by TMK39 and partially shared the acetylated low density lipoprotein cholesterol uptake pathway.
Inflammatory Enteritis
2012, Principles and Practice of Pediatric Infectious Diseases, Fourth Edition

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ReviewPathogenesis of amebiasis

Abstract

Section snippets

Introduction: amebiasis in humans

Determinants of parasite invasiveness

The amoebapore and cytotoxicity

Interaction with intestinal epithelium

RAB proteins

Genomics

Transcription regulation

Encystation and excystation

Conclusions

References and recommended reading

Parasitol Int

Biochim Biophys Acta

Zool Anal Complex Syst

FEBS Letts

Microbes Infect

Mol Biochem Parasitol

Mol Biochem Parasitol

Mol Biochem Parasitol

Protist

Mol Biochem Parasitol

Mol Biochem Parasitol

Parasitol Today

Int J Parasitol

Int J Parasitol

J Biol Chem

J Biol Chem

Curr Opin Microbiol

Mol Biochem Parasitol

Amebiasis in acquired immunodeficiency syndrome

Intern Med

Review
Pathogenesis of amebiasis