Review
Biochemistry & Molecular Biology
Koushik Das, Tomoyoshi Nozaki
Summary: Eukaryotic cells have membrane-enclosed organelles that have distinct functions and characteristics. The distribution and movement of lipids and proteins play a crucial role in determining the identity of each organelle. Studying lipid transport mechanisms in protists, such as Leishmania donovani, can contribute to our understanding of parasitism and eukaryotic evolution. Through bioinformatics analysis, we identified potential lipid transfer proteins in L. donovani and discussed their implications in parasite biology and potential therapeutic targets against visceral leishmaniasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Parasitology
Vikas Kushwaha, Neena Capalash
Summary: This study evaluated the immunomodulatory potential of L. donovani histidyl-tRNA synthetase (LdHisRS) and predicted epitopes using immunoinformatic tools. The results showed that LdHisRS specifically stimulated cell proliferation, nitric oxide release, and cytokine release in vitro, and immunization with LdHisRS resulted in robust immune responses in mice. Additionally, multiple potential epitopes were identified for the development of a multi-epitope vaccine against L. donovani.
Article
Multidisciplinary Sciences
Padmika Madushanka Wadanambi, Uthpali Mannapperuma
Summary: This computational study identified seven phytochemical inhibitors with strong binding affinity to the LdSQS enzyme, showing potential as antileishmanial drugs. These compounds demonstrated favorable physicochemical properties, pharmacokinetic profiles, and toxicity predictions, meeting in silico criteria for oral bioavailability.
Article
Multidisciplinary Sciences
Andreza do Socorro Silva da Veiga, Fernando Tobias Silveira, Edilene Oliveira da Silva, Jose Antonio Picanco Diniz Junior, Sanderson Correa Araujo, Marliane Batista Campos, Andrey Moacir do Rosario Marinho, Geraldo Celio Brandao, Valdicley Vieira Vale, Sandro Percario, Maria Fani Dolabela
Summary: This study evaluated the morphological changes caused by fractions and subfractions obtained from barks of Aspidosperna nitidum against L. (L.) amazonensis promastigotes. The results suggest that alkaloids isolated from A. nitidum show potential as leishmanicidal agents. Scanning electron microscopy and transmission electron microscopy analysis revealed changes in the parasites' morphology after treatment with the active fractions.
SCIENTIFIC REPORTS
(2022)
Article
Parasitology
Smriti Tandon, Rohini Muthuswami, Rentala Madhubala
Summary: Visceral leishmaniasis is a fatal form of leishmaniasis prevalent in the Indian subcontinent. Chemotherapeutic drugs are currently the only means for combating parasitic infections as there are no human licensed vaccines available. Previous studies have identified several amino-acyl tRNA synthetases (aaRS) and associated proteins in Leishmania donovani, which may play a role in novel functions beyond their canonical tRNA aminoacylation role.
Article
Multidisciplinary Sciences
Patrick Lypaczewski, Lovlesh Thakur, Aklank Jain, Sandhya Kumari, Kayla Paulini, Greg Matlashewski, Manju Jain
Summary: Leishmaniasis is a neglected tropical disease with two main types: cutaneous and visceral. Most visceral cases occur in the Indian subcontinent and East Africa due to Leishmania donovani. However, recent outbreaks of cutaneous leishmaniasis in India, such as in Himachal Pradesh, have been found to be caused by atypical phenotypes of L. donovani. Genetic analysis revealed that the strain in Himachal Pradesh is a hybrid of two independent L. donovani parasites from the ISC1 clade, found in the Nepalese highlands.
Article
Microbiology
Bart Cuypers, Pieter Meysman, Ionas Erb, Wout Bittremieux, Dirk Valkenborg, Geert Baggerman, Inge Mertens, Shyam Sundar, Basudha Khanal, Cedric Notredame, Jean-Claude Dujardin, Malgorzata A. Domagalska, Kris Laukens
Summary: Aneuploidy has a significant impact on the transcriptome, proteome, and metabolome of Leishmania donovani, leading to disruptions in stochiometric balances and metabolic differences between aneuploid strains. However, protein complex subunits and non-cytoplasmic proteins show attenuations in dosage effects. The differentially expressed proteins are enriched for those involved in protein metabolism. These findings suggest that aneuploidy in Leishmania can be adaptive and make it an attractive model for studying protein homeostasis in the context of aneuploidy.
Article
Biochemistry & Molecular Biology
Mousumi Sinha, Rahul Jagadeesan, Neeraj Kumar, Satabdi Saha, Gugan Kothandan, Diwakar Kumar
Summary: The study aims to identify potential drugs against Ld-MIPS for preventing the spread of leishmaniasis. Through virtual screening and molecular docking, potential inhibitors with good pharmacokinetic properties were identified and further studied through molecular dynamics simulation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Immunology
Rahat Ali, Shams Tabrez, Sajjadul Kadir Akand, Fazlur Rahman, Atahar Husein, Mohd Arish, Ali S. Alqahtani, Mohammad Z. Ahmed, Mohammad Husain, Abdur Rub
Summary: This study evaluated the antileishmanial potential of sesamol against L. donovani, showing that sesamol inhibits parasite growth and proliferation through induction of reactive oxygen species (ROS), mitochondrial dysfunction, DNA fragmentation, cell cycle arrest, and apoptosis-like cell death. The results suggest the possible use of sesamol for the treatment of leishmaniasis following further in vivo validations.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Karthik Ramalingam, Sonali Gangwar, Deep Chandra Balodi, Apeksha Anand, Shailendra Yadav, Subhasish Biswas, Anil Kumar Karunakaran Sasikala, Kailash Chand Gupta, Sanjay Batra, Neena Goyal
Summary: Chemotherapy is crucial for controlling visceral leishmaniasis, but current regimens have drawbacks. This study identified compound 3c as the lead candidate for treating VL, showing the best in vivo antileishmanial efficacy.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Bandigi Narsimulu, Rahila Qureshi, Pranay Jakkula, Priti Singh, Mohammed Arifuddin, Insaf Ahmed Qureshi
Summary: In this study, the authors purified and characterized seryl tRNA synthetase (LdSerRS) and its mutants in Leishmania donovani. The purified LdSerRS showed high enzymatic activity and a higher content of alpha helices in secondary structure. A mutation in the ATP binding residues resulted in a reduced affinity for cofactor without significant alteration in secondary structure. The researchers identified Comp 5l as a specific inhibitor for leishmanial SerRS, which showed low potency towards purified HsSerRS. Structural analysis revealed the binding of Comp 5l into the cofactor binding site of LdSerRS with high affinity. The study provides a promising approach for developing specific therapeutics targeting leishmanial SerRS.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Ravi Ranjan Kumar, Ravi Jain, Sabir Akhtar, Nidha Parveen, Arabinda Ghosh, Veena Sharma, Shailja Singh
Summary: Vitamin B1 is essential for carbohydrate metabolism, and this study focuses on the enzyme Thiamine Pyrophosphokinase (TPK) and its role in Leishmania donovani, a parasite causing visceral leishmaniasis. In silico and biochemical experiments were conducted to identify and characterize LdTPK, and it was found that inhibiting LdTPK led to growth inhibition of the parasite. These findings suggest that LdTPK could be a potential target for the development of new anti-leishmanial agents.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Immunology
Amrita Das, Mohd. Kamran, Nahid Ali
Summary: The study demonstrates that the liposomal formulation of HO-3867 is effective in inducing apoptosis in Leishmania parasites while being safe for normal murine macrophages. The treatment effectively reduces intracellular L. donovani amastigote burden by inducing parasite killing through ROS and NO activity.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Sergi Burguera, Antonio Frontera, Antonio Bauza
Summary: By combining computations and X-ray structure analysis, we have demonstrated that [Pt(CN4)](2-) can act as a Lewis acid inside an enzyme's cavity. The nature of an unexpected contact between a catalytically active GLN residue in a mitochondrial synthase and the Pt(ii) center was investigated using molecular dynamics and quantum mechanics calculations. The results confirm the electron acceptor role of [Pt(CN4)](2-), which serves as inspiration for designing biomolecular cages that can modify the nucleophilic/electrophilic character of an organometallic compound.
CHEMICAL COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Aretha Chan, Jose-Mauricio Ayala, Fernando Alvarez, Ciriaco Piccirillo, George Dong, David Langlais, Martin Olivier
Summary: This study analyzed the early innate inflammatory events during L. major infection, confirming the significant role of the virulence factor GP63 in providing favorable conditions for host cell infection. The data suggest that GP63 does not greatly influence pathogen-induced inflammatory cell recruitment, but rather affects their activation status and effector function, as well as potentially influencing the internalization of promastigotes during early infection.
Article
Immunology
Alok Kumar Singh, Rajeev Kumar Pandey, Jair Lage Siqueira-Neto, Yong-Jun Kwon, Lucio H. Freitas, Chandrima Shaha, Rentala Madhubala
INFECTION AND IMMUNITY
(2015)
Article
Multidisciplinary Sciences
Sneha Anand, Rentala Madhubala
SCIENTIFIC REPORTS
(2015)
Article
Cell Biology
Alok Kumar Singh, Rajeev Kumar Pandey, Chandrima Shaha, Rentala Madhubala
Article
Biochemistry & Molecular Biology
Sneha Anand, Rentala Madhubala
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Infectious Diseases
Nimisha Mittal, Rohini Muthuswami, Rentala Madhubala
PLOS NEGLECTED TROPICAL DISEASES
(2017)
Article
Infectious Diseases
Sanya Chadha, Ramachandran Vijayan, Sakshi Gupta, Manoj Munde, Samudrala Gourinath, Rentala Madhubala
PLOS NEGLECTED TROPICAL DISEASES
(2018)
Article
Biochemistry & Molecular Biology
Reetika Manhas, Pankaj Tripathi, Sameena Khan, Bhavana Sethu Lakshmi, Shambhu Krishan Lal, Venkatraman Subramanian Gowri, Amit Sharma, Rentala Madhubala
JOURNAL OF BIOLOGICAL CHEMISTRY
(2014)
Article
Biochemistry & Molecular Biology
Nimisha Mittal, Marie Morada, Pankaj Tripathi, V. S. Gowri, Swati Mandal, Alison Quirch, Myung Hee Park, Nigel Yarlett, Rentala Madhubala
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2014)
Article
Infectious Diseases
Ruby Bansal, Shib Sankar Sen, Rohini Muthuswami, Rentala Madhubala
PLOS NEGLECTED TROPICAL DISEASES
(2019)
Article
Multidisciplinary Sciences
Chintalapati Janaki, Venkatraman S. Gowri, Narayanaswamy Srinivasan
Summary: Genome sequencing projects reveal all protein sequences encoded in a genome, but the high evolutionary divergence between homologous proteins poses challenges in detecting distant relationships. Traditional methods are limited, while using multiple PSSMs and cascaded searches can be more effective. Combining principles from different approaches, the 'Master Blaster' protocol significantly enhances the ability to detect remote homologues.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Ruby Bansal, Himanshu Bhusan Samal, V. S. Gowri, Shib Sankar Sen, Indira Ghosh, Rentala Madhubala
PROCEEDINGS OF THE INDIAN NATIONAL SCIENCE ACADEMY
(2017)