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1.
J Zoo Wildl Med ; 52(1): 232-240, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827181

RESUMO

Amoebiasis is a significant protozoal disease of reptiles causing nonspecific clinical signs including diarrhea, anorexia, and lethargy. It frequently results in acute death. Investigation of the pathophysiology of amoebiasis in reptiles has been hampered by the inability to accurately identify amoeba to the species level using conventional techniques. This study reviewed reptile medical records from the Wildlife Conservation Society's archives from 1998 to 2017. Amoebae were identified histologically in 54 cases in 31 different species. Of these, amoebiasis was the cause of death in 32 (18 chelonians, 7 lizards, and 7 snakes), a significant co-morbidity in 14 (six chelonians, two lizards, and six snakes), and seen incidentally in eight cases (one chelonian, six lizards, and one snake). Relocation from one enclosure to another was also evaluated and 65% of cases had been moved within 180 days of death (median 46 days). Frozen tissue samples from 19 of these cases were tested via an Entamoeba (genus-specific) polymerase chain reaction (PCR) assay. PCR products were sequenced and Entamoeba species were identified. Six individuals were positive for Entamoeba invadens (three chelonians, two snakes, one lizard), two for Entamoeba ranarum (both snakes), and one for Entamoeba terrapinae (chelonian); the other 10 cases were negative via PCR. Entamoeba ranarum has typically been considered a disease of amphibians with only one report of disease in a snake. Entamoeba terrapinae has only been reported without associated disease in chelonians. These results suggest that amoebiasis is a complicated and nuanced disease of reptiles, and warrants additional study.


Assuntos
Amebíase/veterinária , Animais de Zoológico , Répteis/parasitologia , Amebíase/epidemiologia , Amebíase/parasitologia , Animais , Estudos Retrospectivos
2.
J Fish Dis ; 44(2): 149-160, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33314290

RESUMO

Amoebic gill disease (AGD) is one of the main health issues impacting farmed Atlantic salmon. Neoparamoeba perurans causes AGD; however, a diversity of other amoeba species colonizes the gills and there is little understanding of whether they are commensal or potentially involved in different stages of gill disease development. Here, we conduct in vivo challenges of naïve Atlantic salmon with cultured Nolandella sp. and Pseudoparamoeba sp. to investigate their pathogenicity to Atlantic salmon gills. Additionally, we assessed whether the presence of Nolandella sp. and Pseudoparamoeba sp. influences the onset and/or severity of N. perurans-induced AGD. All three strains attached and multiplied on the gills according to qPCR analysis. Furthermore, minor gross gill lesions and histological changes were observed post-exposure. While N. perurans was found associated with classical AGD lesions, Nolandella sp. and Pseudoparamoeba sp. were not found associated with lesion sites and these lesions did not meet the expected composite of histopathological changes for AGD. Moreover, the presence of these non-N. perurans species did not significantly increase the severity of AGD. This trial provides evidence that cultured Nolandella sp. and Pseudoparamoeba sp. do not induce AGD and do not influence the severity of AGD during the early stages of development.


Assuntos
Amebíase/parasitologia , Amebozoários/patogenicidade , Doenças dos Peixes/parasitologia , Brânquias/parasitologia , Amebíase/etiologia , Amebíase/patologia , Amebozoários/genética , Amebozoários/parasitologia , Animais , Doenças dos Peixes/etiologia , Doenças dos Peixes/patologia , Reação em Cadeia da Polimerase em Tempo Real , Salmo salar
3.
Exp Parasitol ; 218: 108008, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32979343

RESUMO

Acanthamoeba sp. is a free living amoeba that causes severe, painful and fatal infections, viz. Acanthamoeba keratitis and granulomatous amoebic encephalitis among humans. Antimicrobial chemotherapy used against Acanthamoeba is toxic to human cells and show side effects as well. Infections due to Acanthamoeba also pose challenges towards currently used antimicrobial treatment including resistance and transformation of trophozoites to resistant cyst forms that can lead to recurrence of infection. Therapeutic agents targeting central nervous system infections caused by Acanthamoeba should be able to cross blood-brain barrier. Nanoparticles based drug delivery put forth an effective therapeutic method to overcome the limitations of currently used antimicrobial chemotherapy. In recent years, various researchers investigated the effectiveness of nanoparticles conjugated drug and/or naturally occurring plant compounds against both trophozoites and cyst form of Acanthamoeba. In the current review, a reasonable effort has been made to provide a comprehensive overview of various nanoparticles tested for their efficacy against Acanthamoeba. This review summarizes the noteworthy details of research performed to elucidate the effect of nanoparticles conjugated drugs against Acanthamoeba.


Assuntos
Acanthamoeba/efeitos dos fármacos , Amebicidas/administração & dosagem , Nanopartículas/administração & dosagem , Acanthamoeba/crescimento & desenvolvimento , Ceratite por Acanthamoeba/tratamento farmacológico , Ceratite por Acanthamoeba/parasitologia , Amebíase/tratamento farmacológico , Amebíase/mortalidade , Amebíase/parasitologia , Amebicidas/farmacologia , Amebicidas/uso terapêutico , Biguanidas/administração & dosagem , Biguanidas/farmacologia , Biguanidas/uso terapêutico , Infecções Protozoárias do Sistema Nervoso Central/tratamento farmacológico , Infecções Protozoárias do Sistema Nervoso Central/mortalidade , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Clorexidina/administração & dosagem , Clorexidina/farmacologia , Clorexidina/uso terapêutico , Sistemas de Liberação de Medicamentos , Imunocompetência , Hospedeiro Imunocomprometido , Encefalite Infecciosa/tratamento farmacológico , Encefalite Infecciosa/mortalidade , Encefalite Infecciosa/parasitologia , Nanopartículas/classificação , Nanopartículas/uso terapêutico , Trofozoítos/efeitos dos fármacos
4.
Exp Parasitol ; 218: 107979, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32866583

RESUMO

Balamuthia mandrillaris and Naegleria fowleri are free-living amoebae that can cause life-threatening infections involving the central nervous system. The high mortality rates of these infections demonstrate an urgent need for novel treatment options against the amoebae. Considering that indole and thiazole compounds possess wide range of antiparasitic properties, novel bisindole and thiazole derivatives were synthesized and evaluated against the amoebae. The antiamoebic properties of four synthetic compounds i.e., two new bisindoles (2-Bromo-4-(di (1H-indol-3-yl)methyl)phenol (denoted as A1) and 2-Bromo-4-(di (1H-indol-3-yl)methyl)-6-methoxyphenol (A2)) and two known thiazole (4-(3-Nitrophenyl)-2-(2-(pyridin-3-ylmethylene)hydrazinyl)thiazole (A3) and 4-(Biphenyl-4-yl)-2-(2-(1-(pyridin-4-yl)ethylidene)hydrazinyl)thiazole (A4)) were evaluated against B. mandrillaris and N. fowleri. The ability of silver nanoparticle (AgNPs) conjugation to enrich antiamoebic activities of the compounds was also investigated. The synthetic heterocyclic compounds demonstrated up to 53% and 69% antiamoebic activities against B. mandrillaris and N. fowleri respectively, while resulting in up to 57% and 68% amoebistatic activities, respectively. Antiamoebic activities of the compounds were enhanced by up to 71% and 51% against B. mandrillaris and N. fowleri respectively, after conjugation with AgNPs. These compounds exhibited potential antiamoebic effects against B. mandrillaris and N. fowleri and conjugation of synthetic heterocyclic compounds with AgNPs enhanced their activity against the amoebae.


Assuntos
Amebíase/tratamento farmacológico , Balamuthia mandrillaris/efeitos dos fármacos , Infecções Protozoárias do Sistema Nervoso Central/tratamento farmacológico , Indóis/administração & dosagem , Naegleria fowleri/efeitos dos fármacos , Tiazóis/administração & dosagem , Amebíase/parasitologia , Amebicidas/administração & dosagem , Amebicidas/química , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Células HeLa , Humanos , Indóis/química , Concentração Inibidora 50 , Nanopartículas Metálicas , Tiazóis/química
5.
Parasitol Res ; 119(7): 2327-2335, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32476058

RESUMO

Acanthamoeba castellanii is a free-living amoeba which can cause a blinding keratitis and fatal granulomatous amoebic encephalitis. The treatment of Acanthamoeba infections is challenging due to formation of cyst. Quinazolinones are medicinally important scaffold against parasitic diseases. A library of nineteen new 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives was synthesized to evaluate their antiamoebic activity against Acanthamoeba castellanii. One-pot synthesis of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-ones (1-19) was achieved by reaction of 2-amino-4,5-dimethoxybenzoic acid, trimethoxymethane, and different substituted anilines. These compounds were purified and characterized by standard chromatographic and spectroscopic techniques. Antiacanthamoebic activity of these compounds was determined by amoebicidal, encystation, excystation and host cell cytopathogenicity in vitro assays at concentrations of 50 and 100 µg/mL. The IC50 was found to be between 100 and 50 µg/mL for all the compounds except compound 5 which did not exhibit amoebicidal effects at these concentrations. Furthermore, lactate dehydrogenase assay was also performed to evaluate the in vitro cytotoxicity of these compounds against human keratinocyte (HaCaT) cells. The results revealed that eighteen out of nineteen derivatives of quinazolinones significantly decreased the viability of A. castellanii. Furthermore, eighteen out of nineteen tested compounds inhibited the encystation and excystation, as well as significantly reduced the A. castellanii-mediated cytopathogenicity against human cells. Interestingly, while tested against human normal cell line HaCaT keratinocytes, all compounds did not exhibit any overt cytotoxicity. Furthermore, a detailed structure-activity relationship is also studied to optimize the most potent hit from these synthetic compounds. This report presents several potential lead compounds belonging to 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives for drug discovery against infections caused by Acanthamoeba castellanii.


Assuntos
Acanthamoeba castellanii/efeitos dos fármacos , Amebicidas/química , Amebicidas/farmacologia , Quinazolinonas/química , Quinazolinonas/farmacologia , Acanthamoeba castellanii/crescimento & desenvolvimento , Amebíase/tratamento farmacológico , Amebíase/parasitologia , Amebicidas/síntese química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Encistamento de Parasitas/efeitos dos fármacos , Quinazolinonas/síntese química , Relação Estrutura-Atividade
6.
J Fish Dis ; 43(6): 665-672, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32291787

RESUMO

Gill parasitic infections challenge farming of rainbow trout (Oncorhynchus mykiss, Walbaum) in freshwater facilities. Apart from flagellates (Ichthyobodo, (Pinto) and ciliates (Ichthyophthirius (Fouquet), Ambiphrya (Raabe), Apiosoma (Blanchard), Trichodinella (Sramek-Husek) and Trichodina (Ehrenberg)), we have shown that amoebae are prevalent in Danish trout farms. Gills were isolated from farmed rainbow trout in six fish farms (conventional and organic earth pond and recirculated systems) and placed on non-nutrient agar (NNA) moistened with modified Neff's amoeba saline (AS) (15°C). Gill amoebae from all examined fish colonized the agar and were identified based on morphological criteria showing species within the genera Trinema (Dujardin) (family Trinematidae), Vannella (Bovee) (family Vannellidae). In addition, hartmannellid amoebae were recorded. We established a monoculture of Vannella sp., confirmed the genus identity by PCR and sequencing and performed an in vitro determination of antiparasitic effects (dose-response studies) of various compounds including sodium chloride (NaCl), hydrogen peroxide, peracetic acid, formalin, aqueous garlic and oregano extracts and a Pseudomonas H6 surfactant. All amoebae were killed in concentrations of 16.90 mg/ml (garlic), 17.90 mg/ml (oregano), NaCl (7.5 mg/ml), hydrogen peroxide (100 µg/ml), peracetic acid (0.03 µg/ml), formaldehyde (25 µg/ml) and the Pseudomonas H6 surfactant (250 µg/ml).


Assuntos
Amebíase/veterinária , Antiparasitários/farmacologia , Oncorhynchus mykiss , Tubulinos/efeitos dos fármacos , Amebíase/tratamento farmacológico , Amebíase/parasitologia , Animais , Relação Dose-Resposta a Droga , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/parasitologia , Água Doce , Brânquias/parasitologia , Técnicas In Vitro
7.
Parasitol Res ; 119(4): 1337-1351, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32056023

RESUMO

Amoebiasis is a human intestinal disease caused by the parasite Entamoeba histolytica. It has been previously demonstrated that E. histolytica heat shock protein 70 (EhHSP70) plays an important role in amoebic pathogenicity by protecting the parasite from the dangerous effects of oxidative and nitrosative stresses. Despite its relevance, this protein has not yet been characterized. In this study, the EhHSP70 genes were cloned, and the two recombinant EhHSP70 proteins were expressed, purifying and biochemically characterized. Additionally, after being subjected to some host stressors, the intracellular distribution of the proteins in the parasite was documented. Two amoebic HSP70 isoforms, EhHSP70-A and EhHSP70-B, with 637 and 656 amino acids, respectively, were identified. Kinetic parameters of ATP hydrolysis showed low rates, which were in accordance with those of the HSP70 family members. Circular dichroism analysis showed differences in their secondary structures but similarities in their thermal stability. Immunocytochemistry in trophozoites detected EhHSP70 in the nuclei and cytoplasm as well as a slight overexpression when the parasites were subjected to oxidants and heat. The structural differences of amoebic HSP70s with their human counterparts may be used to design specific inhibitors to treat human amoebiasis.


Assuntos
Entamoeba histolytica/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Isoformas de Proteínas/genética , Amebíase/parasitologia , Animais , Núcleo Celular , Dicroísmo Circular , Clonagem Molecular , Citoplasma/metabolismo , Entamoeba histolytica/patogenicidade , Proteínas de Choque Térmico HSP70/classificação , Humanos , Estrutura Secundária de Proteína , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Análise de Sequência de Proteína , Trofozoítos/metabolismo
8.
J Fish Dis ; 43(1): 39-48, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726482

RESUMO

Hydrogen peroxide (H2 O2 ) is a commonly used treatment for a range of parasitic diseases of marine finfish, including amoebic gill disease (AGD). While this treatment is partially effective at reducing parasite load, H2 O2 can have detrimental effects on the host under certain conditions. Treatment temperature and dose concentration are two factors that are known to influence the toxicity of H2 O2 ; however, their impact on the outcome of AGD treatment remains unclear. Here, we investigated the effects of treatment temperature (8, 12 or 16°C) and dose concentration (750, 1,000, 1,250 mg/L) on the efficacy of H2 O2 to treat AGD. We demonstrated that a 20-min bath treatment of H2 O2 at all doses reduced both parasite load and gross gill score significantly. Parasite load and gross gill score were lowest in the 1,000 mg/L treatment performed at 12°C. At the high dose and temperature combinations, H2 O2 caused moderate gill damage and a significant increase in the plasma concentration of electrolytes (sodium, chloride and potassium). Taken together, our study demonstrates that higher H2 O2 treatment temperatures can adversely affect the host and do not improve the effectiveness of the treatment.


Assuntos
Amebíase/veterinária , Antiprotozoários/uso terapêutico , Doenças dos Peixes/tratamento farmacológico , Peróxido de Hidrogênio/uso terapêutico , Salmo salar , Temperatura , Amebíase/tratamento farmacológico , Amebíase/parasitologia , Animais , Relação Dose-Resposta a Droga , Feminino , Doenças dos Peixes/parasitologia , Brânquias/parasitologia
9.
Lab Med ; 51(2): e20-e26, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31711180

RESUMO

BACKGROUND: Encephalitis is caused by infection, immune mediated diseases, or primary inflammatory diseases. Of all the causative infectious pathogens, 90% are viruses or bacteria. Granulomatous amoebic encephalitis (GAE), caused by Balamuthia mandrillaris, is a rare but life-threatening disease. Diagnosis and therapy are frequently delayed due to the lack of specific clinical manifestations. METHOD: A healthy 2 year old Chinese male patient initially presented with a nearly 2 month history of irregular fever. We present this case of granulomatous amoebic encephalitis caused by B. mandrillaris. Next generation sequencing of the patient's cerebrospinal fluid (CSF) was performed to identify an infectious agent. RESULT: The results of next generation sequencing of the CSF showed that most of the mapped reads belonged to Balamuthia mandrillaris. CONCLUSION: Next generation sequencing (NGS) is an unbiased and rapid diagnostic tool. The NGS method can be used for the rapid identification of causative pathogens. The NGS method should be widely applied in clinical practice and help clinicians provide direction for the diagnosis of diseases, especially for rare and difficult cases.


Assuntos
Amebíase/diagnóstico , Amebíase/patologia , Balamuthia mandrillaris/isolamento & purificação , Infecções Protozoárias do Sistema Nervoso Central/diagnóstico , Infecções Protozoárias do Sistema Nervoso Central/patologia , Encefalite Infecciosa/diagnóstico , Encefalite Infecciosa/patologia , Amebíase/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Líquido Cefalorraquidiano/parasitologia , Pré-Escolar , China , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Encefalite Infecciosa/parasitologia , Masculino , Técnicas de Diagnóstico Molecular/métodos
10.
Acta Parasitol ; 65(1): 36-43, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31571139

RESUMO

PURPOSE: Free-living amoeba (FLA) including Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria are among the soil-born parasites. There are reports of FLA-related keratitis with a history of contact with soil and dust sources, particularly among the farmers. Due to lack of the previous studies on the farmland soils and a limited number of researches conducted on recreational soils in Iran, the present study was conducted. METHODS: A total of 93 soil samples including farming lands and recreational places were tested for the presence of Acanthamoeba spp. Balamuthia mandrillaris, Naegleria, and Vermamoeba using morphological key and sequencing-based tools. Pathogenicity of Acanthamoeba positive strains was also evaluated. To verify genetic associations and taxonomic status of isolated amoeba, a phylogenetic tree was built by MEGA 5.05 software inferred by the 18S rRNA gene based on maximum likelihood algorithm. RESULTS: Overall, 28 samples (30%) were contaminated with potentially pathogenic FLA, and according to the sequencing data, 17 strains were successfully sequenced. The isolated Acanthamoeba belonged to T2, T4, T5, mixed T4 and T5 contaminations, and T11. ITS sequencing revealed the occurrence of one strain of Naegleria canariensis. Four strains of Vermamoeba vermiformis were also confirmed. Morphological survey and PCR assay failed to show any positive results for Balamuthia mandrillaris. Pathogenic potential of the Acanthamoeba strains showed that T2, T4, and T11 genotypes were highly pathogenic, whereas T5 genotypes demonstrated lower pathogenic potential. CONCLUSION: The results indicate that soil could be a serious hazard to human health, and therefore, further studies are expected to investigate the source of infection in patients developing FLA-related diseases. The present study is the first to investigate FLA in the farmland soils in Iran and the first to report the presence of N. canariensis in the country.


Assuntos
Amoeba/classificação , Fazendas/estatística & dados numéricos , Genótipo , Filogenia , Solo/parasitologia , Acanthamoeba/classificação , Acanthamoeba/isolamento & purificação , Amebíase/epidemiologia , Amebíase/parasitologia , Amoeba/isolamento & purificação , Amoeba/patogenicidade , DNA de Protozoário/genética , Humanos , Irã (Geográfico)/epidemiologia , Naegleria/classificação , Naegleria/isolamento & purificação , Parques Recreativos , Saúde Pública , RNA Ribossômico 18S/genética , Abastecimento de Água
11.
Int J Med Microbiol ; 310(1): 151358, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31587966

RESUMO

Amoebiasis is a parasitic disease caused by Entamoeba histolytica (E. histolytica), an extracellular enteric protozoan. This infection mainly affects people from developing countries with limited hygiene conditions, where it is endemic. Infective cysts are transmitted by the fecal-oral route, excysting in the terminal ileum and producing invasive trophozoites (amoebae). E. histolytica mainly lives in the large intestine without causing symptoms; however, possibly as a result of so far unknown signals, the amoebae invade the mucosa and epithelium causing intestinal amoebiasis. E. histolytica possesses different mechanisms of pathogenicity for the adherence to the intestinal epithelium and for degrading extracellular matrix proteins, producing tissue lesions that progress to abscesses and a host acute inflammatory response. Much information has been obtained regarding the virulence factors, metabolism, mechanisms of pathogenicity, and the host immune response against this parasite; in addition, alternative treatments to metronidazole are continually emerging. An accesible and low-cost diagnostic method that can distinguish E. histolytica from the most nonpathogenic amoebae and an effective vaccine are necessary for protecting against amoebiasis. However, research about the disease and its prevention has been a challenge due to the relationship between E. histolytica and the host during the distinct stages of the disease is multifaceted. In this review, we analyze the interaction between the parasite, the human host, and the colon microbiota or pathogenic microorganisms, which together give rise to intestinal amoebiasis.


Assuntos
Amebíase/parasitologia , Países em Desenvolvimento , Disenteria Amebiana/parasitologia , Intestinos/parasitologia , Saúde Pública , Amebíase/tratamento farmacológico , Amebíase/epidemiologia , Animais , Antiprotozoários/uso terapêutico , Disenteria Amebiana/epidemiologia , Entamoeba histolytica/imunologia , Entamoeba histolytica/patogenicidade , Fezes/parasitologia , Microbioma Gastrointestinal , Interações Hospedeiro-Patógeno , Humanos , Intestinos/microbiologia , Metronidazol/uso terapêutico , Camundongos , Virulência
13.
Artigo em Inglês | MEDLINE | ID: mdl-31707263

RESUMO

The free-living amebae Naegleria, Acanthamoeba, and Balamuthia cause rare but life-threatening infections. All three parasites can cause meningoencephalitis. Acanthamoeba can also cause chronic keratitis and both Balamuthia and Acanthamoeba can cause skin and systemic infections. There are minimal drug development pipelines for these pathogens despite a lack of available treatment regimens and high fatality rates. To identify anti-amebic drugs, we screened 159 compounds from a high-value repurposed library against trophozoites of the three amebae. Our efforts identified 38 compounds with activity against at least one ameba. Multiple drugs that bind the ATP-binding pocket of mTOR and PI3K are active, highlighting these compounds as important inhibitors of these parasites. Importantly, 24 active compounds have progressed at least to phase II clinical studies and overall 15 compounds were active against all three amebae. Based on central nervous system (CNS) penetration or exceptional potency against one amebic species, we identified sixteen priority compounds for the treatment of meningoencephalitis caused by these pathogens. The top five compounds are (i) plicamycin, active against all three free-living amebae and previously U.S. Food and Drug Administration (FDA) approved, (ii) TG02, active against all three amebae, (iii and iv) FDA-approved panobinostat and FDA orphan drug lestaurtinib, both highly potent against Naegleria, and (v) GDC-0084, a CNS penetrant mTOR inhibitor, active against at least two of the three amebae. These results set the stage for further investigation of these clinically advanced compounds for treatment of infections caused by the free-living amebae, including treatment of the highly fatal meningoencephalitis.


Assuntos
Acanthamoeba/efeitos dos fármacos , Amebíase/tratamento farmacológico , Amebozoários/efeitos dos fármacos , Antiprotozoários/farmacologia , Infecções Protozoárias do Sistema Nervoso Central/tratamento farmacológico , Naegleria/efeitos dos fármacos , Amebíase/parasitologia , Carbazóis/farmacologia , Carbazóis/uso terapêutico , Técnicas de Cultura de Células , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Meios de Cultura , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Concentração Inibidora 50 , Oxazinas/farmacologia , Oxazinas/uso terapêutico , Panobinostat/farmacologia , Panobinostat/uso terapêutico , Plicamicina/farmacologia , Plicamicina/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico
14.
Parasitol Res ; 118(10): 3061-3066, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31502076

RESUMO

The burden of HIV/AIDS in Iran is not as high as in the other countries with high prevalence; however, the number of cases of HIV/AIDs is increasing in this region. According to a recent report, Iran had 5000 (1400-13,000) new cases of HIV infection with 4000 (2500-6200) AIDS-related deaths. Individuals affected by HIV/AIDS are highly susceptible for developing opportunistic infections, e.g. the cerebral complications related to pathogenic free-living amoebae and colonization of free-living amoebae (FLA) can be a serious hazard for patients living with HIV/AIDS. In the present study, a total of 70 oral and nasal mucosal samples were obtained from HIV/AIDS patients referred to the reference hospitals in Iran and tested for the presence of potentially pathogenic FLA using culture and PCR/sequencing-based methods. To discern the taxonomic status of Acanthamoeba genotypes a maximum likelihood phylogenetic tree was constructed and tolerance assays were performed for the positive Acanthamoeba strains. Among the patients with HIV/AIDS referred to the reference hospitals from 2017 to 2019, 7.1% were found positive for pathogenic free-living amoebae. Three strains (HA3, HA4, and HA5) belonged to the T4 genotype, one strain (HA1) was related to the T5 genotype assigned as A. lenticulata, and another strain (HA2) had high homology to Vermamoeba vermiformis. The tolerance assay used for Acanthamoeba strains (HA1, HA3, and HA4) classified these amoebae as highly pathogenic strains. For the most part, the encephalitis cases occurring in HIV/AIDS patients in Iran remain undiagnosed due to lack of awareness of the practitioners on the available diagnostic tools for this lethal infection; therefore, the true incidence of GAE in this region is unknown. A possible colonization with FLA should be considered in the differential diagnosis of suspected cases of CNS infections among HIV/AIDS patients. This study is the first worldwide comprehensive study attempting to isolate and identify the FLA colonization in HIV/AIDS patients. This study highlights the fact that clinicians should be aware of the differential diagnosis of cerebral disease related to FLA in patients with HIV/AIDS.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Acanthamoeba/classificação , Acanthamoeba/isolamento & purificação , Amebíase/parasitologia , Mucosa Bucal/parasitologia , Filogenia , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Acanthamoeba/genética , Acanthamoeba/patogenicidade , Adulto , Idoso , Amebíase/complicações , Amebíase/epidemiologia , Feminino , Genótipo , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/parasitologia
15.
Photodiagnosis Photodyn Ther ; 28: 166-171, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31499180

RESUMO

BACKGROUND: Microbial keratitis is a potential cause of corneal blindness. We investigated the amoebicidal efficacy of photodynamic antimicrobial therapy with a light-emitting diode as the light source and the cationic chlorin derivative TONS504 as the photosensitizer for the elimination of Acanthamoeba, a causative organism of corneal infection and blindness. Acanthamoeba keratitis remains a challenge to treat because of limited available treatments. METHODS: Acanthamoeba castellani 50370 was exposed to TONS504 at various concentrations (0, 1, or 10 mg/L for trophozoites; 0, 1, 10, or 20 mg/L for cysts), irradiated at various light energies (0, 10, or 30 J/cm2 for trophozoites; 0, 30, or 60 J/cm2 for cysts), and incubated at 26 °C for 3 h. Assessment of cell viability by trypan blue staining revealed that photodynamic antimicrobial therapy attenuated the survival of trophozoites and cysts dependent on TONS504 concentration and light energy. RESULTS: Photodynamic antimicrobial therapy with 10 mg/L TONS504 and 30 J/cm2 light energy suppressed trophozoite viability by 77%, and 20 mg/L TONS504 and 60 J/cm2 light energy attenuated cyst survival by 42%. Staining with fluorescein isothiocyanate-conjugated annexin V and ethidium homodimer III revealed photodynamic antimicrobial therapy induced apoptosis and necrosis in trophozoites dependent upon the intensity of treatment, whereas apoptosis was the predominant form of cell death in cysts. CONCLUSIONS: Photodynamic antimicrobial therapy with TONS504 warrants further investigation as a potential treatment modality for Acanthamoeba keratitis.


Assuntos
Amebíase/tratamento farmacológico , Ceratite/tratamento farmacológico , Ceratite/parasitologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Acanthamoeba castellanii/efeitos dos fármacos , Amebíase/parasitologia , Amebicidas/farmacologia , Animais , Oocistos/efeitos dos fármacos , Trofozoítos/efeitos dos fármacos
16.
Sci Rep ; 9(1): 11651, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31406269

RESUMO

Recently, the search for novel therapeutic agents against Acanthamoeba species has been focused on the evaluation of natural resources. Among them, marine microorganisms have risen as a source of bioactive compounds with the advantage of the ability to obtain unlimited and constant amounts of the compounds in contrast to other natural sources such as plants. Furthermore, marine actinomycetes have recently been reported as highly rich in bioactive agents including salinosporamides, xiamycines, indolocarbazoles, naphtyridines, phenols, dilactones such as antimycines and macrolides among others. In this study, staurosporine (STS) was isolated from a strain of Streptomyces sanyensis and tested against Acanthamoeba to characterize the therapeutic potential of STS against this protozoan parasite. We have established that STS is active against both stages of the Acanthamoeba life cycle, by the activation of Programmed Cell Death via the mitochondrial pathway of the trophozoite. We have also established that STS has relatively low toxicity towards a macrophage cell line. However, previous studies have highlighted higher toxicity levels induced on other vertebrate cell lines and future research to lower these toxicity issues should be developed.


Assuntos
Acanthamoeba castellanii/efeitos dos fármacos , Amebicidas/farmacologia , Organismos Aquáticos/química , Estaurosporina/farmacologia , Streptomyces/química , Acanthamoeba castellanii/citologia , Amebíase/tratamento farmacológico , Amebíase/parasitologia , Amebicidas/isolamento & purificação , Amebicidas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Macrófagos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Estaurosporina/isolamento & purificação , Estaurosporina/uso terapêutico , Testes de Toxicidade Aguda , Trofozoítos/citologia , Trofozoítos/efeitos dos fármacos
17.
Infect Immun ; 87(11)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31427448

RESUMO

Entamoeba histolytica is an anaerobic parasitic protozoan and the causative agent of amoebiasis. E. histolytica expresses proteins that are structurally homologous to human proteins and uses them as virulence factors. We have previously shown that E. histolytica binds exogenous interferon gamma (IFN-γ) on its surface, and in this study, we explored whether exogenous IFN-γ could modulate parasite virulence. We identified an IFN-γ receptor-like protein on the surface of E. histolytica trophozoites by using anti-IFN-γ receptor 1 (IFN-γR1) antibody and performing immunofluorescence, Western blot, protein sequencing, and in silico analyses. Coupling of human IFN-γ to the IFN-γ receptor-like protein on live E. histolytica trophozoites significantly upregulated the expression of E. histolytica cysteine protease A1 (EhCP-A1), EhCP-A2, EhCP-A4, EhCP-A5, amebapore A (APA), cyclooxygenase 1 (Cox-1), Gal-lectin (Hgl), and peroxiredoxin (Prx) in a time-dependent fashion. IFN-γ signaling via the IFN-γ receptor-like protein enhanced E. histolytica's erythrophagocytosis of human red blood cells, which was abrogated by the STAT1 inhibitor fludarabine. Exogenous IFN-γ enhanced chemotaxis of E. histolytica, its killing of Caco-2 colonic and Hep G2 liver cells, and amebic liver abscess formation in hamsters. These results demonstrate that E. histolytica expresses a surface IFN-γ receptor-like protein that is functional and may play a role in disease pathogenesis and/or immune evasion.


Assuntos
Entamoeba histolytica/metabolismo , Proteínas de Protozoários/metabolismo , Receptores de Interferon/química , Amebíase/imunologia , Amebíase/parasitologia , Animais , Células CACO-2 , Sobrevivência Celular , Cricetinae , Células Hep G2 , Humanos , Interferon gama/farmacologia , Masculino , Fagocitose , Proteínas de Protozoários/química , Proteínas de Protozoários/genética
20.
J Fish Dis ; 42(9): 1241-1258, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31206728

RESUMO

A relationship between increasing water temperature and amoebic gill disease (AGD) prevalence in Atlantic salmon (Salmo salar) has been noted at fish farms in numerous countries. In Scotland (UK), temperatures above 12°C are considered to be an important risk factor for AGD outbreaks. Thus, the purpose of this study was to test for the presence of an association between temperature and variation in the severity of AGD in Atlantic salmon at 10 and 15°C. The results showed an association between temperature and variation in AGD severity in salmon from analysis of histopathology and Paramoeba perurans load, reflecting an earlier and stronger infection post-amoebae exposure at the higher temperature. While no significant difference between the two temperature treatment groups was found in plasma cortisol levels, both glucose and lactate levels increased when gill pathology was evident at both temperatures. Expression analysis of immune- and stress-related genes showed more modulation in gills than in head kidney, revealing an organ-specific response and an interplay between temperature and infection. In conclusion, temperature may not only affect the host response, but perhaps also favour higher attachment/growth capacity of the amoebae as seen with the earlier and stronger P. perurans infection at 15°C.


Assuntos
Amebíase/veterinária , Brânquias/patologia , Temperatura Alta/efeitos adversos , Salmo salar , Amebíase/parasitologia , Amebíase/patologia , Animais , Doenças dos Peixes/parasitologia , Doenças dos Peixes/patologia
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