Review
Pharmacology & Pharmacy
Swati Lamba, Amit Roy
Summary: DNA topoisomerases are enzymes found in all organisms, including unicellular protozoan parasites. The structural, expression, and functional differences between protozoan topoisomerases and human topoisomerases make them important targets for drug development. Understanding the structure-function relationship of parasitic topoisomerases is crucial for the development of potent anti-parasitic drugs.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Cell Biology
Justin A. Davis, Andres V. Reyes, Arpita Saha, Donald J. Wolfgeher, Shou-Ling Xu, Andrew W. Truman, Bibo Li, Kausik Chakrabarti
Summary: Telomerase is an enzyme responsible for maintaining the telomeres of chromosomes. It consists of two main components, telomerase reverse transcriptase (TERT) and telomerase RNA (TR). TR, a long non-coding RNA, provides the template for telomeric DNA synthesis. In this study, the interactome of TbTERT from Trypanosoma brucei was identified, revealing unique interactions and suggesting differences in telomere maintenance compared to other eukaryotes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Chemistry, Analytical
Mahsa Feyziazar, Mohammad Amini, Ali Jahanban-Esfahlan, Behzad Baradaran, Fatemeh Oroojalian, Amin Kamrani, Ahad Mokhtarzadeh, Jafar Soleymani, Miguel de la Guardia
Summary: Protozoan parasites play a significant role in causing various human diseases and can be transmitted through different routes. Conventional diagnostic methods have limitations, while biosensor technologies offer rapid, sensitive, and selective detection, which can have a significant impact on disease control and drug evaluation.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2022)
Article
Entomology
Mariana Cancian, Tiago Minuzzi Freire da Fontoura Gomes, Elgion Lucio Silva Loreto
Summary: Transposable elements, specifically the mariner element, can promote somatic mobilization in fruit flies, leading to a high rate of somatic insertion. Temperature is an important factor in the increase of mariner element somatic mobilization.
Review
Biochemistry & Molecular Biology
Chi Zhang, Hao Jiang, Hanlin Jiang, Hui Xi, Baodong Chen, Yubing Liu, Mario Juhas, Junyi Li, Yang Zhang
Summary: Infectious and parasitic diseases pose a major threat to public health, and deep learning has shown remarkable performance in the diagnosis of protozoan parasites through microscopic examination. However, challenges and future trends still exist for deep learning in protozoan parasite diagnosis.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Parasitology
Suellen Rodrigues Maran, Krista Fleck, Natalia Melquie Monteiro-Teles, Tony Isebe, Pegine Walrad, Victoria Jeffers, Igor Cestari, Elton J. R. Vasconcelos, Nilmar Moretti
Summary: Protein lysine acetylation is a major regulatory post-translational modification across different organisms, affecting chromatin structure, gene expression, and various cellular processes. The discovery of acetylomes in protozoan parasites suggests that acetylation may regulate crucial biological processes in these parasites. Furthermore, the regulation of glycolytic enzymes by acetylation in protozoans indicates the potential role of this modification in regulating other processes essential for parasite survival and adaptation during their life cycle.
TRENDS IN PARASITOLOGY
(2021)
Review
Immunology
Anita Leocadio Freitas-Mesquita, Andre Luiz Araujo Dos-Santos, Jose Roberto Meyer-Fernandes
Summary: Leishmania parasites depend on various protein phosphatases to adapt, survive, and proliferate inside their hosts, including overcoming host immune responses. These phosphatases also play important roles in parasite virulence, drug resistance, and modulation of host immune responses. Through regulation of gene expression and enzymatic activity, phosphatases are crucial for the lifecycle and pathogenicity of Leishmania parasites.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Microbiology
Veronica Jimenez, Sebastian Mesones
Summary: Ion channels play a crucial role in protozoan parasites, but their study is challenging due to methodological difficulties. Understanding the function of ion channels in protozoan parasites is of great importance for the development of new therapeutic strategies.
Review
Immunology
Magda Reyes-Lopez, Beatriz Aguirre-Armenta, Carolina Pina-Vazquez, Mireya de la Garza, Jesus Serrano-Luna
Summary: Protozoan diseases pose a significant global health concern, causing millions of infections and deaths annually and leading to major socioeconomic problems. Iron is crucial for microbial survival, and human pathogenic parasites have developed mechanisms to obtain iron and amino acids from hemoglobin present in the host. This review provides an overview of the hemoglobin and heme-uptake mechanisms utilized by these parasites to survive inside the host.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Karolina Kot, Natalia Lanocha-Arendarczyk, Michal Ptak, Aleksandra Lanocha, Elzbieta Kalisinska, Danuta Kosik-Bogacka
Summary: This review discusses the biochemical and molecular mechanisms in kidneys infected with protozoan parasites like Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Acanthamoeba spp. Pathomechanisms of Leishmania spp. and Plasmodium spp. infections have been deeply investigated, providing insight into novel treatments, while Toxoplasma gondii and Acanthamoeba spp. infections in the kidneys require further research to understand their mechanisms. Gaps in the pathophysiology of renal toxoplasmosis and acanthamoebiasis are highlighted, indicating the need for more studies in this area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Shanshan Wang, France Moreau, Kris Chadee
Summary: Gasdermins (GSDMs) are a group of proteins that can induce cell death or pyroptosis by forming pores in the plasma membrane. This review provides a comprehensive overview of the expression, activation, biological functions, and regulation of GSDMs, with a focus on their role in host defense against Eh and other protozoan parasitic infections.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Naiwen Zhang, Ning Jiang, Liying Yu, Tiandong Guan, Xiaoyu Sang, Ying Feng, Ran Chen, Qijun Chen
Summary: The study provides the first comprehensive investigation of lactylated sites in Trypanosoma brucei, revealing the regulatory roles of protein lactylation in energy metabolism and gene expression in this parasite. It was found that glucose metabolism critically regulates protein lactylation in T. brucei, and a unique lactate production pathway is involved in the decrease of protein lactylation levels when glucose concentration increases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Parasitology
Milena Svobodova, Ivan Cepicka, Lenka Zidkova, Aysheshm Kassahun, Jan Votypka, Lubomir Peske, Kristyna Hrazdilova, Jana Brzonova, Petr Vorisek, Karel Weidinger
Summary: The study on blood parasites in the breeding population of Eurasian sparrowhawk in Prague reveals high parasite diversity and turnover among individuals.
PARASITES & VECTORS
(2023)
Article
Biology
Isabell Berneburg, Stefan Rahlfs, Katja Becker, Karin Fritz-Wolf
Summary: In this study, the crystal structure of Leishmania donovani G6PD (LdG6PD) was determined, revealing differences in the N-terminal domain compared to related Trypanosoma G6PDs. Functional investigations showed that the N-domain of LdG6PD is involved in the formation of a tetramer, which is unique to Leishmania species. Furthermore, the binding mode of LdG6PD was analyzed, demonstrating an ordered mechanism confirmed by domain shift and rotation. These findings contribute to the understanding of the molecular mechanisms of G6PDs and provide insights for drug discovery.
COMMUNICATIONS BIOLOGY
(2022)
Article
Immunology
Poonam Keshav, Deepak Kumar Goyal, Sukhbir Kaur
Summary: This study focused on evaluating the antiparasitic activity and immunomodulatory effects of ellagic acid (EA) against L. donovani. The in vitro study showed that EA had parasiticidal activity and halted cell cycle progression. In vivo experiments demonstrated that EA reduced parasite burden and increased specific T cell populations, enhancing the immune response. EA was found to be safe and non-toxic in cell lines and mice.
MEDICAL MICROBIOLOGY AND IMMUNOLOGY
(2023)
Review
Genetics & Heredity
Jeziel D. Damasceno, Catarina A. Marques, Jennifer Black, Emma Briggs, Richard McCulloch
Summary: Genomes are read and copied during growth and development, purposely altered to adapt cellular behavior and drive evolution. Kinetoplastids demonstrate a wide range of genome activities that affect their adaptability and biology.
TRENDS IN GENETICS
(2021)
Article
Cell Biology
Hellida Marina Costa-Silva, Bruno Carvalho Resende, Adriana Castilhos Souza Umaki, Willian Prado, Marcelo Santos da Silva, Stela Virgilio, Andrea Mara Macedo, Sergio Danilo Junho Pena, Erich Birelli Tahara, Luiz Ricardo Orsini Tosi, Maria Carolina Elias, Luciana Oliveira Andrade, Joao Luis Reis-Cunha, Gloria Regina Franco, Stenio Perdigao Fragoso, Carlos Renato Machado
Summary: DNA topoisomerases, in particular topoisomerase 3 alpha, play crucial roles in genomic maintenance, cell growth, and DNA damage response in Trypanosoma cruzi. Knockout of topoisomerase 3 alpha affects parasite growth, invasion rates, and ability to repair DNA damage induced by genotoxic agents. These findings underscore the importance of topoisomerase 3 alpha in homologous recombination repair and replication stress in T. cruzi.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Hongjie Guo, Sebastian Damerow, Luciana Penha, Stefanie Menzies, Gloria Polanco, Hicham Zegzouti, Michael A. J. Ferguson, Stephen M. Beverley
Summary: This study identified a mitochondrial fucosyltransferase, FUT1, in the trypanosomatid parasite Leishmania, which is essential for cell viability. The enzyme showed a broad fucosyltransferase activity and its mitochondrial localization was crucial for normal growth and mitochondrial function. Mitochondrial FUT1s in trypanosomatids may be used to study mitochondrial glycosylation and could be a potential target for chemotherapy against these serious human pathogens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Gabriel L. A. Silva, Luiz R. O. Tosi, Richard McCulloch, Jennifer Ann Black
Summary: Cells activate and coordinate various DNA repair pathways in response to DNA lesions to preserve genome integrity, collectively known as the DNA damage response (DDR). Kinetoplastidae exhibit peculiarities in core biological processes, such as unique DNA repair pathways and multigenic transcription advantages. Recent studies have implicated ATR and ATM kinases in the DDR of kinetoplastid parasites, raising questions about the conservation and functions of DNA repair kinases in these organisms.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Microbiology
Angela M. A. Velasquez, Paula J. Bartlett, Irwin A. P. Linares, Thais G. Passalacqua, Daphne D. L. Teodoro, Kely B. Imamura, Stela Virgilio, Luiz R. O. Tosi, Aline de Lima Leite, Marilia A. R. Buzalaf, Jecika M. Velasques, Adelino V. G. Netto, Andrew P. Thomas, Marcia A. S. Graminha
Summary: The study elucidates the mechanisms of action of an antileishmanial complex, which induces oxidative stress, cell cycle arrest, and apoptotic-like features in the parasite. Additionally, the complex shows effectiveness in reducing parasite load in Leishmania-infected rodents, suggesting its potential application in treating both cutaneous and visceral forms of the disease.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Immunology
Raissa Bernardes da Silva, Willian dos Reis Bertoldo, Lucila Langoni Naves, Fernanda Bernadelli de Vito, Jeziel Dener Damasceno, Luiz Ricardo Orsini Tosi, Carlos Renato Machado, Andre Luiz Pedrosa
Summary: In this study, the DNA damage response pathways in promastigote forms of L. major were investigated. The overexpression of LmjEXO1 made the cells more susceptible to genotoxic damage, while ATR-specific inhibition made the control cells more susceptible to oxidative damage.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
F. Matthew Kuhlmann, Phillip N. Key, Suzanne M. Hickerson, John Turk, Fong-Fu Hsu, Stephen M. Beverley
Summary: Leishmania parasites can survive without synthesizing sphingolipids themselves, instead salvaging and metabolizing sphingolipids from the host to produce inositol phosphorylceramide (IPC). This calls into question the suitability of targeting IPC synthesis for chemotherapy and suggests that targeting the salvage and catabolism of host sphingolipids may be a more effective approach.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Infectious Diseases
Michael A. Mandell, Wandy L. Beatty, Stephen M. Beverley
Summary: Leishmania parasites undergo a transformation from motile stage to non-motile stage upon infecting mammalian host cells. This process, known as amastigogenesis, is characterized by several landmark events. The expression of a virulence factor called LPG varies in different host cell types, indicating its role in promoting infectivity.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Microbiology
Jacquelyn R. McDonald, Bryan C. Jensen, Aakash Sur, Iris L. K. Wong, Stephen M. Beverley, Peter J. Myler
Summary: This study reveals the abundant distribution of histone variants and PTMs in the chromatin landscape of Leishmania tarentolae, contributing to our understanding of the epigenetic markers associated with transcription, DNA replication, and chromosome segregation in these early diverging eukaryotes.
Article
Microbiology
Tiago R. Ferreira, Ehud Inbar, Jahangheer Shaik, Brendan M. Jeffrey, Kashinath Ghosh, Deborah E. Dobson, Stephen M. Beverley, David Sacks
Summary: Leishmania, a parasitic protozoa that causes various diseases collectively known as leishmaniases, has been found to undergo sexual reproduction inside the sand fly vector midgut. This study provides the first high resolution, whole-genome sequencing analysis of self-mating in Leishmania, revealing that self-hybridization can occur with comparable frequency as interstrain mating under experimental lab conditions, leading to important genomic alterations that can potentially take place within every naturally infected sand fly.
Review
Immunology
Jennifer A. Black, Joao Luis Reis-Cunha, Angela. K. Cruz, Luiz. R. O. Tosi
Summary: Leishmania is able to rapidly adjust gene expression by modifying gene copy number, using the products of genome instability. However, how Leishmania regulate genome plasticity to enhance fitness while avoiding toxic overexpression of co-amplified and co-transcribed genes remains unclear.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Genetics & Heredity
Lon-Fye Lye, Katherine L. Owens, Soojin Jang, Joseph E. Marcus, Erin A. Brettmann, Stephen M. Beverley
Summary: RNA interference (RNAi) is a powerful tool for functional genetic tests and has been successfully applied to the study of L. braziliensis. We developed RNAi knockdown constructs using Gateway(TM) recombinase technology and found that the efficacy of RNAi increased with stem length. Co-selection for RNAi against APRT1 using APP could enhance the efficacy of RNAi against reporter constructs.
Article
Microbiology
Gloria Polanco, Nichollas E. Scott, Lon F. Lye, Stephen M. Beverley
Summary: This study leveraged an ultradeep proteomic approach to investigate two virulence-associated genes in Leishmania, revealing significant quantitative differences and phenotypic changes linked to LPG2 or FUT1. The work advanced knowledge by identifying potential proteins underlying persistence-without-pathology phenotype and mitochondrial dysfunction in mutants, shedding light on new therapeutic targets.
MICROBIOLOGY SPECTRUM
(2022)
Review
Parasitology
Ana Paula Menezes, Ana Milena Murillo, Camila Gachet de Castro, Natalia Karla Bellini, Luiz Ricardo Orsini Tosi, Otavio Henrique Thiemann, Maria Carolina Elias, Ariel Mariano Silber, Julia Pinheiro Chagas da Cunha
Summary: Epigenetic marks are chemical modifications on chromatin-associated proteins and nucleic acids that affect gene expression. The connection between metabolism and epigenetics has been increasingly discovered, revealing how the environment influences gene regulation and phenotype diversity. This review speculates and proposes associations between epigenetics and metabolism in trypanosomes, which are protozoan parasites causing human and livestock diseases.
TRENDS IN PARASITOLOGY
(2023)
Article
Microbiology
Gloria Polanco, Nichollas E. Scott, Lon F. Lye, Stephen M. Beverley
Summary: This study utilizes an ultradeep proteomic approach to analyze two virulence-associated genes in Leishmania, revealing their impact on mitochondrial proteins and secretory pathways. Additionally, the study did not find evidence of protein fucosylation, suggesting that the target of the vital protein may be more complex.
MICROBIOLOGY SPECTRUM
(2022)
