scholarly journals In SilicoStudy ofLeishmania donovaniα-βTubulin and Inhibitors

2014 ◽  
Vol 2014 ◽  
pp. 1-8
Author(s):  
Tamiris M. Assis ◽  
Daiana T. Mancini ◽  
Teodorico C. Ramalho ◽  
Elaine F. F. da Cunha
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Severe Form ◽  
Important Target ◽  
Loop Domain

Leishmania donovaniis a parasite that causes visceral leishmaniasis, a severe form of leishmaniasis that affects vital organs. An important target for the treatment of this disease is the proteinα-βtubulin, which was modeled in this paper and proposed as a target for the treatment of visceral leishmaniasis. Two classes of compounds were studied, dinitroanilines and oxadiazoles. According to the docking results, dinitroanilines interact better with the L loop domain and oxadiazoles interact better with the colchicine domain.

scholarly journals Hepatomegaly Associated with Non-Obstructive Sinusoidal Dilation in Experimental Visceral Leishmaniasis

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1356
Author(s):  
Kota Maeda ◽  
Sonya Sadoughi ◽  
Ayako Morimoto ◽  
Kazuyuki Uchida ◽  
James K. Chambers ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Thrombus Formation ◽  
Clinical Manifestations ◽  
Liver Weight ◽  
Severe Form ◽  
Tissue Water ◽  
Cell Accumulation ◽  
Sinusoidal Endothelium ◽  
Biochemical Analyses

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis caused by protozoan parasites of the genus Leishmania. Hepatomegaly is one of the most frequent clinical manifestations of VL, whereas immunopathology of the symptom has not been well investigated. Using our chronic model of experimental VL, we examined the influence of Leishmania donovani infection on the liver by clinical, histological, and biochemical analyses. The infected mice showed increased liver weight 24 weeks post-infection. Although an increase in serum ALT and inflammatory cell accumulation were observed in the livers of infected mice, no apparent parenchymal necrosis or fibrosis was observed. Tissue water content analyses demonstrated that increased liver weight was predominantly due to an increase in water weight. Together with the finding of hepatic sinusoidal dilation, these results suggested that edema associated with sinusoidal dilation causes hepatomegaly in L. donovani infection. Immunostaining of platelets and erythrocytes showed no thrombus formation or damage to the sinusoidal endothelium in the liver of infected mice. Taken together, these results suggest that hepatomegaly during experimental VL is caused by non-obstructive sinusoidal dilation.

Immune induction by adjuvanted Leishmania donovani vaccines against the visceral leishmaniasis in BALB/c mice

Immunobiology ◽  
2021 ◽  
Vol 226 (2) ◽  
pp. 152057
Author(s):  
Deepak Kumar Goyal ◽  
Poonam Keshav ◽  
Sukhbir Kaur
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani

scholarly journals Clinical and laboratory profiles of visceral leishmaniasis among adult patients admitted to Felege Hiwot Hospital, Bahir Dar, Ethiopia

2021 ◽  
Vol 9 ◽  
pp. 205031212110367
Author(s):  
Berhanu Tarekegn ◽  
Ayanaw Tamene
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Clinical Presentation ◽  
Winter Season ◽  
Adult Patients ◽  
Sand Fly ◽  
Timely Initiation ◽  
Vector Borne Disease ◽  
Vector Borne ◽  
Endemic Areas

Background: Visceral leishmaniasis is a vector-borne disease caused by Leishmania donovani transmitted by sand fly species. It is the third most common vector-borne disease globally. Visceral leishmaniasis is endemic in Ethiopia with an estimated annual incidence ranging from 3700 to 7400 cases. This research aimed to assess the clinical presentations and laboratory profiles of visceral leishmaniasis for early diagnosis and timely initiation of management. Objective: To describe the clinical and laboratory manifestation and diagnostic modalities of visceral leishmaniasis among adult patients admitted to Felege Hiwot Hospital, from 1 September 2016 to 30 August 2019. Method: Institution-based retrospective cross-sectional study was conducted among 141 patients admitted to Felege Hiwot Hospital from 1 September 2016 to 30 August 2019. Descriptive statistics were used to describe the clinical presentation and laboratory profiles of patients with visceral leishmaniasis. Results: Among a total of 141 enrolled patients in the study, males were affected 13-fold. Most of them were travelers to endemic areas during the winter season for labor work. The mean duration of illness was 48 days. Common symptoms were fever (96.5%), weightless (82.5%), jaundice (18.4%), vomiting/diarrhea (13.5%), and bleeding episodes (11.3%). Splenomegaly was seen in 98.6%, ascites in 35.5%, and lymphadenopathy in 9.9%. Lymphadenopathy was seen significantly in HIV patients (40%). Anemia was seen in 95%, thrombocytopenia in 90.2%, leukopenia in 86.4%, and pancytopenia in 79.4%. Half of the patients had coinfection. Neutropenic sepsis was seen in 21.3%. The diagnosis was made by tissue aspiration in 65% of patients. Conclusion: The majority of patients who were diagnosed to have visceral leishmaniasis were young male adults who traveled to the endemic areas seasonally. Fever and splenomegaly were seen as the commonest clinical presentation. Lymphadenopathy occurred in high frequency among HIV co-infected patients. Anemia was the commonest hematologic finding.

scholarly journals Hemophagocytosis in Experimental Visceral Leishmaniasis by Leishmania donovani

2016 ◽  
Vol 10 (3) ◽  
pp. e0004505 ◽  
Author(s):  
Ayako Morimoto ◽  
Satoko Omachi ◽  
Yasutaka Osada ◽  
James K. Chambers ◽  
Kazuyuki Uchida ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani

Diagnosis and Causative Species of Visceral Leishmaniasis in Southwest Saudi Arabia

2021 ◽  
Author(s):  
Aymen Abdelhaleem ◽  
Nabil Dhayhi ◽  
Mohamed Salih Mahfouz ◽  
Ommer Daffalla ◽  
Mansour Mubarki ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Visceral Leishmaniasis ◽  
Real Time ◽  
Real Time Pcr ◽  
Leishmania Donovani ◽  
Target Genes ◽  
Sample Volume ◽  
Pcr Products ◽  
Polymerase Chain ◽  
Robust Evidence

Visceral leishmaniasis (VL) is the most severe clinical form of the disease and has been reported in the Jazan region of southwest Saudi Arabia. This study aimed to diagnose VL by real-time polymerase chain reaction (PCR) and the direct agglutination test (DAT) and to identify the causative Leishmania species. A total of 80 participants, including 30 suspected VL patients, 30 healthy endemic control individuals, and 20 malaria disease controls, were enrolled in this study. Blood samples were collected and tested for Leishmania DNA by real-time PCR and for antibody by the DAT. Sequencing of some amplified PCR products was used to identify the causative Leishmania species. The diagnosis of VL was successfully achieved by both real-time PCR and by DAT with 100% sensitivity. Leishmania donovani and Leishmania infantum species were detected by sequencing both by the kDNA and ITS1 target genes, followed a BLASTn search. The detection of VL antibody by the DAT followed by the confirmatory detection of Leishmania DNA in patient blood by PCR could promote the adoption of the much less invasive and more sensitive methods for the routine diagnosis of VL. Further study with high sample volume to evaluate the PCR and the DAT are needed, to generate more robust evidence. Based on the sequencing results, emerging studies on VL should focus on the causative Leishmania species, reservoirs, and vectors that are important in the study area.

scholarly journals Genetic Validation of Leishmania donovani Lysyl-tRNA Synthetase Shows that It Is Indispensable for Parasite Growth and Infectivity

mSphere ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Sanya Chadha ◽  
N. Arjunreddy Mallampudi ◽  
Debendra K. Mohapatra ◽  
Rentala Madhubala
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Essential Gene ◽  
Protozoan Parasite ◽  
Protein Translation ◽  
Trna Synthetase ◽  
Parasite Growth ◽  
Coding Sequences ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases

ABSTRACT Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis. Increasing resistance and severe side effects of existing drugs have led to the need to identify new chemotherapeutic targets. Aminoacyl-tRNA synthetases (aaRSs) are ubiquitous and are required for protein synthesis. aaRSs are known drug targets for bacterial and fungal pathogens. Here, we have characterized and evaluated the essentiality of L. donovani lysyl-tRNA synthetase (LdLysRS). Two different coding sequences for lysyl-tRNA synthetases are annotated in the Leishmania genome database. LdLysRS-1 (LdBPK_150270.1), located on chromosome 15, is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 (LdBPK_300130.1), present on chromosome 30, is closer to bacteria. In the present study, we have characterized LdLysRS-1. Recombinant LdLysRS-1 displayed aminoacylation activity, and the protein localized to the cytosol. The LdLysRS-1 heterozygous mutants had a restrictive growth phenotype and attenuated infectivity. LdLysRS-1 appears to be an essential gene, as a chromosomal knockout of LdLysRS-1 could be generated when the gene was provided on a rescuing plasmid. Cladosporin, a fungal secondary metabolite and a known inhibitor of LysRS, was more potent against promastigotes (50% inhibitory concentration [IC50], 4.19 µM) and intracellular amastigotes (IC50, 1.09 µM) than were isomers of cladosporin (3-epi-isocladosporin and isocladosporin). These compounds exhibited low toxicity to mammalian cells. The specificity of inhibition of parasite growth caused by these inhibitors was further assessed using LdLysRS-1 heterozygous mutant strains and rescue mutant promastigotes. These inhibitors inhibited the aminoacylation activity of recombinant LdLysRS. Our data provide a framework for the development of a new class of drugs against this parasite. IMPORTANCE Aminoacyl-tRNA synthetases are housekeeping enzymes essential for protein translation, providing charged tRNAs for the proper construction of peptide chains. These enzymes provide raw materials for protein translation and also ensure fidelity of translation. L. donovani is a protozoan parasite that causes visceral leishmaniasis. It is a continuously proliferating parasite that depends heavily on efficient protein translation. Lysyl-tRNA synthetase is one of the aaRSs which charges lysine to its cognate tRNA. Two different coding sequences for lysyl-tRNA synthetases (LdLysRS) are present in this parasite. LdLysRS-1 is closer to apicomplexans and eukaryotes, whereas LdLysRS-2 is closer to bacteria. Here, we have characterized LdLysRS-1 of L. donovani. LdLysRS-1 appears to be an essential gene, as the chromosomal null mutants did not survive. The heterozygous mutants showed slower growth kinetics and exhibited attenuated virulence. This study also provides a platform to explore LdLysRS-1 as a potential drug target.

scholarly journals Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10–Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani

2018 ◽  
Vol 201 (11) ◽  
pp. 3362-3372 ◽  
Author(s):  
Patrick T. Bunn ◽  
Marcela Montes de Oca ◽  
Fabian de Labastida Rivera ◽  
Rajiv Kumar ◽  
Susanna S. Ng ◽  
...  
Keyword(s):  
T Cells ◽  
Visceral Leishmaniasis ◽  
Regulatory T Cells ◽  
Leishmania Donovani ◽  
Immunoregulatory Mechanisms
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