-
Antimicrobial Agents and Chemotherapy Jun 2022Infection with pathogenic free-living amoebae, including Naegleria fowleri, spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because...
Infection with pathogenic free-living amoebae, including Naegleria fowleri, spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because of catastrophic central nervous system involvement. Efficacious treatment options for these infections are lacking, and the mortality rate due to infection is high. Previously, we evaluated the N. fowleri glucokinase (Glck) as a potential target for therapeutic intervention, as glucose metabolism is critical for viability. Here, we extended these studies to the glucokinases from two other pathogenic free-living amoebae, including Acanthamoeba castellanii (Glck) and (Glck). While these enzymes are similar (49.3% identical at the amino acid level), they have distinct kinetic properties that distinguish them from each other. For ATP, Glck and Glck have apparent values of 472.5 and 41.0 μM, while Homo sapiens Glck (Glck) has a value of 310 μM. Both parasite enzymes also have a higher apparent affinity for glucose than the human counterpart, with apparent values of 45.9 μM (Glck) and 124 μM (Glck) compared to ~8 mM for Glck. Additionally, Glck and Glck differ from each other and other Glcks in their sensitivity to small molecule inhibitors, suggesting that inhibitors with pan-amoebic activity could be challenging to generate.
Topics: Acanthamoeba; Amebiasis; Amoeba; Balamuthia mandrillaris; Glucokinase; Humans; Naegleria fowleri
PubMed: 35604214
DOI: 10.1128/aac.02373-21 -
ACS Chemical Neuroscience Jun 2023is a pathogenic amoeba that causes a fulminant and rapidly progressive disease affecting the central nervous system called primary amoebic meningoencephalitis (PAM)....
is a pathogenic amoeba that causes a fulminant and rapidly progressive disease affecting the central nervous system called primary amoebic meningoencephalitis (PAM). Moreover, the disease is fatal in more than 97% of the reported cases, mostly affecting children and young people after practicing aquatic activities in nontreated fresh and warm water bodies contaminated with these amoebae. Currently, the treatment of primary amoebic meningoencephalitis is based on a combination of different antibiotics and antifungals, which are not entirely effective and lead to numerous side effects. In the recent years, research against PAM is focused on the search of novel, less toxic, and fully effective antiamoebic agents. Previous studies have reported the activity of cyano-substituted molecules in different protozoa. Therefore, the activity of 46 novel synthetic cyanomethyl vinyl ethers (QOET-51 to QOET-96) against two type strains of (ATCC 30808 and ATCC 30215) was determined. The data showed that QOET-51, QOET-59, QOET-64, QOET-67, QOET-72, QOET-77, and QOET-79 were the most active molecules. In fact, the selectivity index (CC/IC) was sixfold higher when compared to the activities of the drugs of reference. In addition, the mechanism of action of these compounds was studied, with the aim to demonstrate the induction of a programmed cell death process in .
Topics: Child; Humans; Adolescent; Naegleria fowleri; Central Nervous System Protozoal Infections; Amoeba; Ethers
PubMed: 37167960
DOI: 10.1021/acschemneuro.3c00110 -
Scientific Reports Jul 2022Coronamoeba villafranca gen. nov. sp. nov. is a small amoeba isolated from the surface planktonic biotope in the Bay of Villefranche (Mediterranean Sea). It has a...
Coronamoeba villafranca gen. nov. sp. nov. is a small amoeba isolated from the surface planktonic biotope in the Bay of Villefranche (Mediterranean Sea). It has a confusing set of morphological and molecular characters. Its locomotive form is subcylindrical and monopodial with monoaxial cytoplasmic flow and occasional hyaline bulging at the anterior edge (a monotactic morphotype). Based on this set of characters, this amoeba is most similar to members of the genus Nolandella (Tubulinea, Euamoebida). However, molecular phylogenetic analysis based on only the small subunit ribosomal RNA (SSU rRNA) gene and on two concatenated markers (SSU rRNA gene and actin) robustly places this species in the Discosea, specifically, in a clade with Dermamoeba and Paradermamoeba (Dermamoebida) as the closest described relatives, and several SSU rRNA clones from environmental DNA. A unique glycocalyx of the studied amoeba consisting of complex separate units with pentameric symmetry may be considered a unifying character of this species with other dermamoebids. The monotactic morphotype demonstrated by these amoebae primarily occurs in Tubulinea but was recently confirmed in other clades of Amoebozoa (e.g. Dactylopodida and Variosea). This morphotype may be the plesiomorphic mode of cell organization in Amoebozoa that might have evolved in the last amoebozoan common ancestor (LACA) and conserved in several lineages of this group. It may reflect basic characteristics of the cytoskeletal structure and functions in Amoebozoa.
Topics: Amoeba; Amoebozoa; Lobosea; Mediterranean Sea; Phylogeny
PubMed: 35869259
DOI: 10.1038/s41598-022-16721-2 -
Microbiology (Reading, England) May 2018Not long ago, protists were considered one of four eukaryote kingdoms, but recent gene-based phylogenies show that they contribute to all nine eukaryote subdomains. The... (Review)
Review
Not long ago, protists were considered one of four eukaryote kingdoms, but recent gene-based phylogenies show that they contribute to all nine eukaryote subdomains. The former kingdoms of animals, plants and fungi are now relegated to lower ranks within subdomains. Most unicellular protists respond to adverse conditions by differentiating into dormant walled cysts. As cysts, they survive long periods of starvation, drought and other environmental threats, only to re-emerge when conditions improve. For protists pathogens, the resilience of their cysts can prevent successful treatment or eradication of the disease. In this context, effort has been directed towards understanding the molecular mechanisms that control encystation. We here firstly summarize the prevalence of encystation across protists and next focus on Amoebozoa, where most of the health-related issues occur. We review current data on processes and genes involved in encystation of the obligate parasite Entamoeba histolytica and the opportunistic pathogen Acanthamoeba. We show how the cAMP-mediated signalling pathway that controls spore and stalk cell encapsulation in Dictyostelium fruiting bodies could be retraced to a stress-induced pathway controlling encystation in solitary Amoebozoa. We highlight the conservation and prevalence of cAMP signalling genes in Amoebozoan genomes and the suprisingly large and varied repertoire of proteins for sensing and processing environmental signals in individual species.
Topics: Amoebozoa; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Eukaryota; Parasite Encystment; Phylogeny; Protozoan Proteins; Signal Transduction; Spores, Protozoan; Stress, Physiological
PubMed: 29620506
DOI: 10.1099/mic.0.000653 -
Pathogens and Global Health Sep 2023FLA-related conditions are a rare medical occurrence. Despite their rarity, they are considered a public health concern for two reasons: the absence of a regular... (Review)
Review
FLA-related conditions are a rare medical occurrence. Despite their rarity, they are considered a public health concern for two reasons: the absence of a regular treatment regimen in the case of central nervous system infections and the fast progression of the symptoms leading to fatal outcomes. A total of 358 articles were retrieved from different databases (91 from PubMed, 26 from NCBI, 138 from Academia, 102 from Science Direct, and one from IJMED). 7 (46.6%) clinical cases came from Egypt, 2 (13.3%) cases of FLA infection came from Nigeria, 3 (20%) cases came from the Gambia, and 1 (6.6%) case was reported from African countries like Algeria, Tunisia, South Africa, and Zambia. Medical conditions caused by free-living amoeba are considered significant public health concerns. These ubiquitous organisms can cause both fatal and debilitating health conditions. Immediate diagnosis of cases and proper hygienic practices are necessary to provide direct medical intervention. They may be the key to reducing the morbidity and mortality rates from FLA-acquired infections. Although several government-led initiatives have been implemented to mitigate a plethora of parasitic diseases, the case of FLA-related conditions in African countries has yet to be realized.
Topics: Humans; Acanthamoeba; Amebiasis; Amoeba; Public Health; Nigeria
PubMed: 36562083
DOI: 10.1080/20477724.2022.2160890 -
Current Opinion in Biotechnology Oct 2022The identification of novel platform organisms for the production and discovery of small molecules is of high interest for the pharmaceutical industry. In particular,... (Review)
Review
The identification of novel platform organisms for the production and discovery of small molecules is of high interest for the pharmaceutical industry. In particular, the structural complexity of most natural products with therapeutic potential restricts an industrial production since chemical syntheses often require complex multistep routes. The amoeba Dictyostelium discoideum can be easily cultivated in bioreactors due to its planktonic growth behavior and contains numerous polyketide and terpene synthase genes with only a few compounds being already elucidated. Hence, the amoeba both bears a wealth of hidden natural products and allows for the development of new bioprocesses for existing pharmaceuticals. In this mini review, we present D. discoideum as a novel platform for the production of complex secondary metabolites and discuss its suitability for industrial processes. We also provide initial insights into future bioprocesses, both involving bacterial coculture setups and for the production of plant-based pharmaceuticals.
Topics: Amoeba; Bacteria; Biological Products; Dictyostelium; Pharmaceutical Preparations
PubMed: 35944344
DOI: 10.1016/j.copbio.2022.102766 -
The Journal of Eukaryotic Microbiology Jul 2022The alternative oxidase (AOX) is a protein involved in supporting enzymatic reactions of the Krebs cycle in instances when the canonical (cytochrome-mediated)...
The alternative oxidase (AOX) is a protein involved in supporting enzymatic reactions of the Krebs cycle in instances when the canonical (cytochrome-mediated) respiratory chain has been inhibited, while allowing for the maintenance of cell growth and necessary metabolic processes for survival. Among eukaryotes, alternative oxidases have dispersed distribution and are found in plants, fungi, and protists, including Naegleria ssp. Naegleria species are free-living unicellular amoeboflagellates and include the pathogenic species of N. fowleri, the so-called "brain-eating amoeba." Using a multidisciplinary approach, we aimed to understand the evolution, localization, and function of AOX and the role that plays in Naegleria's biology. Our analyses suggest that AOX was present in last common ancestor of the genus and structure prediction showed that all functional residues are also present in Naegleria species. Using cellular and biochemical techniques, we also functionally characterize N. gruberi's AOX in its mitochondria, and we demonstrate that its inactivation affects its proliferation. Consequently, we discuss the benefits of the presence of this protein in Naegleria species, along with its potential pathogenicity role in N. fowleri. We predict that our findings will spearhead new explorations to understand the cell biology, metabolism, and evolution of Naegleria and other free-living relatives.
Topics: Eukaryota; Mitochondrial Proteins; Naegleria; Naegleria fowleri; Oxidoreductases; Plant Proteins
PubMed: 35322502
DOI: 10.1111/jeu.12908 -
Genes Aug 2019The epithelium represents the first and most extensive line of defence against pathogens, toxins and pollutant agents in humans. In general, pathogens have developed... (Review)
Review
The epithelium represents the first and most extensive line of defence against pathogens, toxins and pollutant agents in humans. In general, pathogens have developed strategies to overcome this barrier and use it as an entrance to the organism. , and spp. are amoebae mainly responsible for intestinal dysentery, meningoencephalitis and keratitis, respectively. These amoebae cause significant morbidity and mortality rates. Thus, the identification, characterization and validation of molecules participating in host-parasite interactions can provide attractive targets to timely intervene disease progress. In this work, we present a compendium of the parasite adhesins, lectins, proteases, hydrolases, kinases, and others, that participate in key pathogenic events. Special focus is made for the analysis of assorted molecules and mechanisms involved in the interaction of the parasites with epithelial surface receptors, changes in epithelial junctional markers, implications on the barrier function, among others. This review allows the assessment of initial host-pathogen interaction, to correlate it to the potential of parasite invasion.
Topics: Acanthamoeba; Animals; Entamoeba histolytica; Epithelial Cells; Host-Parasite Interactions; Humans; Naegleria fowleri; Protozoan Infections
PubMed: 31416298
DOI: 10.3390/genes10080618 -
Molecular Biology and Evolution Sep 2017Amoebozoa is the eukaryotic supergroup sister to Obazoa, the lineage that contains the animals and Fungi, as well as their protistan relatives, and the breviate and...
Amoebozoa is the eukaryotic supergroup sister to Obazoa, the lineage that contains the animals and Fungi, as well as their protistan relatives, and the breviate and apusomonad flagellates. Amoebozoa is extraordinarily diverse, encompassing important model organisms and significant pathogens. Although amoebozoans are integral to global nutrient cycles and present in nearly all environments, they remain vastly understudied. We present a robust phylogeny of Amoebozoa based on broad representative set of taxa in a phylogenomic framework (325 genes). By sampling 61 taxa using culture-based and single-cell transcriptomics, our analyses show two major clades of Amoebozoa, Discosea, and Tevosa. This phylogeny refutes previous studies in major respects. Our results support the hypothesis that the last common ancestor of Amoebozoa was sexual and flagellated, it also may have had the ability to disperse propagules from a sporocarp-type fruiting body. Overall, the main macroevolutionary patterns in Amoebozoa appear to result from the parallel losses of homologous characters of a multiphase life cycle that included flagella, sex, and sporocarps rather than independent acquisition of convergent features.
Topics: Amoeba; Amoebozoa; Animals; Biological Evolution; Eukaryota; Evolution, Molecular; Fungi; Gene Library; Invertebrates; Phylogeny; Sequence Analysis, DNA
PubMed: 28505375
DOI: 10.1093/molbev/msx162 -
The Korean Journal of Parasitology Aug 2019Acanthamoeba, one of free-living amoebae (FLA), remains a high risk of direct contact with this protozoan parasite which is ubiquitous in nature and man-made... (Review)
Review
Acanthamoeba, one of free-living amoebae (FLA), remains a high risk of direct contact with this protozoan parasite which is ubiquitous in nature and man-made environment. This pathogenic FLA can cause sight-threatening amoebic keratitis (AK) and fatal granulomatous amoebic encephalitis (GAE) though these cases may not commonly be reported in our clinical settings. Acanthamoeba has been detected from different environmental sources namely; soil, water, hot-spring, swimming pool, air-conditioner, or contact lens storage cases. The identification of Acanthamoeba is based on morphological appearance and molecular techniques using PCR and DNA sequencing for clinico-epidemiological purposes. Recent treatments have long been ineffective against Acanthamoeba cyst, novel anti-Acanthamoeba agents have therefore been extensively investigated. There are efforts to utilize synthetic chemicals, lead compounds from medicinal plant extracts, and animal products to combat Acanthamoeba infection. Applied nanotechnology, an advanced technology, has shown to enhance the anti-Acanthamoeba activity in the encapsulated nanoparticles leading to new therapeutic options. This review attempts to provide an overview of the available data and studies on the occurrence of pathogenic Acanthamoeba among the Association of Southeast Asian Nations (ASEAN) members with the aim of identifying some potential contributing factors such as distribution, demographic profile of the patients, possible source of the parasite, mode of transmission and treatment. Further, this review attempts to provide future direction for prevention and control of the Acanthamoeba infection.
Topics: Acanthamoeba; Amebiasis; Asia, Southeastern; Soil; Water
PubMed: 31533401
DOI: 10.3347/kjp.2019.57.4.341