Article
Chemistry, Medicinal
Helenita C. Quadros, Aysun Capci, Lars Herrmann, Sarah D'Alessandro, Diana Fontinha, Raquel Azevedo, Wilmer Villarreal, Nicoletta Basilico, Miguel Prudencio, Svetlana B. Tsogoeva, Diogo R. M. Moreira
Summary: The artemisinin-quinoline hybrid compound 163A shows potent activity against the asexual blood stage of Plasmodium, with low cytotoxicity and high selectivity for mammalian cells. It suppresses hepatic infection and decreases gametocyte viability, potentially blocking malaria transmission. The bitopic ligand property of the hybrid enhances inhibition of beta-hematin and is essential for arresting the growth of asexual blood parasites.
Article
Microbiology
Danielle Stanisic, Mei-Fong Ho, Reshma Nevagi, Emily Cooper, Maddison Walton, Md Tanjir Islam, Waleed M. Hussein, Mariusz Skwarczynski, Istvan Toth, Michael F. Good
Summary: Malaria vaccine research has shifted towards whole-parasite vaccines, which present a broad repertoire of antigens to the immune system to limit antigenic polymorphism. This study developed an enhanced liposomal vaccine that induced protective immune responses in mice and strong cellular immune responses, making significant progress towards evaluating the vaccine in clinical trials.
Article
Medicine, Research & Experimental
Christine S. Hopp, Sachie Kanatani, Nathan K. Archer, Robert J. Miller, Haiyun Liu, Kevin K. Chiou, Lloyd S. Miller, Photini Sinnis
Summary: This study provides the first characterization of P. falciparum sporozoites in vivo and compares their motility in mouse skin and human skin xenografts with two rodent malaria species. The findings suggest that the skin is not a species-specific barrier for Plasmodium, and antibodies targeting sporozoites significantly impact their motility in mouse skin. The research showcases a potential in vivo platform that could aid in preclinical screening of next-generation vaccines for human malaria parasites.
EMBO MOLECULAR MEDICINE
(2021)
Article
Immunology
Adriano Franco, Yevel Flores-Garcia, Fidel Zavala, David J. Sullivan
Summary: In the acidic lysosome-like digestive vacuole, Plasmodium parasites crystallize heme from hemoglobin into hemozoin, or malaria pigment. Upon release of progeny merozoites, the residual hemozoin is phagocytized by macrophages principally in the liver and spleen where the heme crystals can persist for months to years, as heme oxygenase does not readily degrade the crystal. Hemozoin modulation of monocytes and macrophages has been demonstrated in previous studies. This study shows that purified washed hemozoin decreases P. berghei liver levels and provides innate immune protection against Plasmodium liver stages.
INFECTION AND IMMUNITY
(2023)
Article
Infectious Diseases
John Oludele Olanlokun, Mercy Toluwase Ekundayo, Oluwakemi Ebenezer, Neil Anthony Koorbanally, Olufunso Olabode Olorunsogo
Summary: The African Mistletoe plant has anti-malarial properties, with its hexane fraction showing excellent efficacy against both susceptible and resistant strains of malaria parasites. It reduces parasite load, improves hematological parameters, increases heme, and decreases hemozoin content in infected mice. Friedelan-3-one, a major component, may be responsible for this activity.
INFECTION AND DRUG RESISTANCE
(2021)
Review
Immunology
Abhijit A. Ambegaonkartk, Prasida Holla, Brian Lp Dizon, Haewon Sohn, Susan K. Pierce
Summary: The study highlights the importance of understanding atypical B cells (ABCs) in the defense against infectious diseases. ABCs in chronic infectious diseases and autoimmune diseases have common drivers of differentiation and expansion, with disease-specific features. Comparing ABC populations in malaria-endemic areas and SLE patients can provide insights into developing vaccines that induce pathogen-specific antibody responses and prevent autoimmunity.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Article
Chemistry, Medicinal
Jessica Poole, Lauren E. Hartley-Tassell, Christopher J. Day, Danielle Stanisic, Penny L. Groves, Sumana Chakravarty, B. Kim Lee Sim, Stephen L. Hoffman, Joe Tiralongo, Nicolai Bovin, Denise L. Doolan, Michael P. Jennings
Summary: The transmission of Plasmodium spp. sporozoites to the mammalian host is crucial for the development of malaria, yet the exact route of transmission and the host glycan structures involved are not fully understood. By analyzing the glycan structures recognized and bound by sporozoites from P. falciparum and P. yoelii, this study identified key host glycan structures for human and rodent Plasmodium spp. sporozoites. Understanding how these sporozoites interact with specific glycan structures could offer insight into the infectious disease and aid in the development of effective therapeutics.
ACS INFECTIOUS DISEASES
(2021)
Article
Pharmacology & Pharmacy
Caroline De Souza Pereira, Helenita Costa Quadros, Samuel Yaw Aboagye, Diana Fontinha, Sarah D'Alessandro, Margaret Elizabeth Byrne, Mathieu Gendrot, Isabelle Fonta, Joel Mosnier, Diogo Rodrigo M. Moreira, Nicoletta Basilico, David. L. L. Williams, Miguel Prudencio, Bruno Pradines, Maribel Navarro
Summary: Hybrid-based drugs linked through a transition metal, such as the novel compound [AuAQPQ]PF6, show strong and effective antiplasmodial activity against multiple stages of the Plasmodium life cycle. The compound's mechanism involves inhibiting beta-hematin formation and enzymatic activity of thioredoxin reductases.
Article
Biology
Abhinay Ramaprasad, Severina Klaus, Olga Douvropoulou, Richard Culleton, Arnab Pain
Summary: Through extensive genetic and phenotype analysis of P. vinckei, it was found that the five subspecies have diverged widely and undergone large-scale genome rearrangements. Region-specific selection pressures were observed particularly on genes involved in mosquito transmission. The highland forest subspecies P. v. vinckei has a smaller genome and reduced multigene family repertoire, making it suitable for transfection and ideal for reverse genetics research. Amenable to genetic crosses, P. vinckei isolates show a large degree of phenotypic and genotypic diversity. Their inclusion in studies provides new insights into the evolution of RMPs and multigene families, making them valuable resources for research on parasite virulence and immunogenicity.
Article
Microbiology
Aditya Anand, Manjunatha Chandana, Sourav Ghosh, Rahul Das, Nalini Singh, Pradeep Mini Vaishalli, Nagavara Prasad Gantasala, Govindarajan Padmanaban, Viswanathan Arun Nagaraj
Summary: Food vacuoles of the malaria parasite play a central role in the degradation of red blood cell hemoglobin and detoxification of heme. The deletion of amino acid transporter 1 in Plasmodium berghei leads to swollen food vacuoles, reduced hemozoin production, and resistance to antimalarials. Mice infected with transporter-deleted parasites are protected from cerebral malaria and show delayed transmission.
MICROBIOLOGY SPECTRUM
(2023)
Review
Chemistry, Multidisciplinary
Vitoria Baptista, Mariana S. Costa, Carla Calcada, Miguel Silva, Jose Pedro Gil, Maria Isabel Veiga, Susana O. Catarino
Summary: Early and effective malaria diagnosis is crucial for disease control and prevention of severe cases and deaths. Current diagnostic methods have limitations and there is a need for simpler, faster, and more accurate alternative methods. Hemozoin, as a biomarker for malaria detection, has unique features and is being explored for new label-free diagnostic methods.
Article
Microbiology
Renu Sudhakar, Navin Adhikari, Saniya Pamnani, Abhipsa Panda, Manish Bhattacharjee, Zeba Rizvi, Sadaf Shehzad, Dinesh Gupta, Puran Singh Sijwali
Summary: Despite the challenges posed by drug-resistant parasite strains, repurposing existing drugs for malaria treatment is an attractive option. Bazedoxifene, a selective estrogen receptor modulator, has shown potent inhibitory activity against Plasmodium falciparum and Plasmodium berghei. It inhibits the formation of hemozoin, a byproduct of hemoglobin degradation by the malaria parasite, and could potentially be repurposed as an antimalarial drug.
MICROBIOLOGY SPECTRUM
(2022)
Article
Materials Science, Multidisciplinary
Janeth Perez-Garza, Emily Parrish-Mulliken, Zachary Deane, Linnaea E. Ostroff
Summary: Electron microscopy (EM) volume reconstruction is a powerful tool for studying brain circuits, but integrating molecular information is challenging. Cryofixation can preserve morphology and allows indefinite sample storage, but compromises membrane integrity when using antibody labeling. We developed a method using cryofixation that allows sensitive immunolabeling, preserves ultrastructure, and is compatible with high-contrast staining for serial EM reconstruction.
MICROSCOPY AND MICROANALYSIS
(2023)
Article
Spectroscopy
Jessica J. Y. Ong, Jeonghun Oh, Xiang Yong Ang, Renugah Naidu, Trang T. T. Chu, Jae Hyoung Im, Umar Manzoor, Tuyet Kha Nguyen, Seok-Won Na, Eun-Taek Han, Christeen Davis, Won Sun Park, Wanjoo Chun, Hojong Jun, Se Jin Lee, Sunghun Na, Jerry K. Y. Chan, YongKeun Park, Bruce Russell, Rajesh Chandramohanadas, Jin-Hee Han
Summary: In this study, a label-free tomographic technique was used to visualize the remodeling process of host red blood cells (RBC) during malaria parasite infection and quantify the changes in biochemical properties. The results provided quantitative information about the influence of the host cell environment on the growth, survival, and replication of P. falciparum and P. vivax in their respective host cells. These precise three-dimensional measurements of infected red cells demonstrate the potential of evolving 3D imaging to advance our understanding of Plasmodium biology and host-parasite interactions.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2023)
Article
Pharmacology & Pharmacy
Jerome Dormoi, Remy Amalvict, Mathieu Gendrot, Bruno Pradines
Summary: The untreated malaria can quickly progress to severe forms, and drug resistance poses a threat to malaria protection efforts worldwide. Therefore, the development of new chemotherapy is necessary. This study contributes new data on the use of methylene blue (MB) in combination with common antimalarial drugs for the treatment of malaria and cerebral malaria. The results show that the combination of MB and AQ is a good candidate for preventing cerebral malaria.
Article
Microbiology
Maira Turiel-Silva, Camila Wendt, Edilene O. Silva, Ana Paula Drummond Rodrigues, Wanderley de Souza, Kildare Miranda, Jose A. P. Diniz
Summary: This study utilized electron microscopy and tomography to reconstruct the three-dimensional structure of C. lignieresi-infected red blood cells, revealing the remodeling of erythrocytes induced by the parasite and providing new insights into its parasitic mechanism.
JOURNAL OF EUKARYOTIC MICROBIOLOGY
(2022)
Article
Microscopy
Marcia Attias, Juliana C. Vidal, Carmem S. A. Takata, Marta Campaner, Erney P. Camargo, Marta M. G. Teixeira, Wanderley De Souza
Summary: The ultrastructural study of a new trypanosome isolated from a toad in Brazil revealed unique features such as a complex cytostome-cytopharynx structure and abundant organelles, making it a potential model for research on endocytosis and lipid storage.
Article
Parasitology
A. A. Alves, C. L. Alcantara, M. V. A. Dantas-Jr, J. D. Sunter, W. De Souza, N. L. Cunha-e-Silva
Summary: The study investigated the dynamics of the orphan myosin MyoF in Trypanosoma cruzi, finding changes in localization during the cell cycle and metacyclogenesis. Detergent fractionation and immunolocalization experiments indicated MyoF's presence in the SPC microtubules. The data suggest that MyoF may have a role throughout the endocytic pathway, not just at the cargo entry site.
PARASITOLOGY INTERNATIONAL
(2022)
Article
Microbiology
Giulia Maria Pires dos Santos, Luana Pereira Borba-Santos, Taissa Vila, Isabella Dib Ferreira Gremiao, Sandro Antonio Pereira, Wanderley De Souza, Sonia Rozental
Summary: Sporotrichosis is a common subcutaneous fungal infection caused by direct inoculation of Sporothrix spp. from soil to the skin. Cats play an important role in the zoonotic transmission of sporotrichosis in hot-spot endemic areas like Brazil. Biofilms formed by Sporothrix yeasts contribute to the recurrence of infection and resistance to antifungal drugs like itraconazole. Miltefosine shows potential as an off-label alternative to itraconazole by demonstrating antibiofilm activity against Sporothrix biofilms.
Article
Microbiology
Allan C. de Azevedo-Martins, Kary Ocana, Wanderley de Souza, Ana Tereza Ribeiro de Vasconcelos, Marta M. G. Teixeira, Erney P. Camargo, Joao M. P. Alves, Maria Cristina M. Motta
Summary: The symbiotic relationship between trypanosomatids and bacteria involves extensive metabolic exchanges, with the bacteria providing essential metabolic pathways for the protozoan. An in-silico study found that most genes involved in glycerophospholipid production are only present in the Symbiont Harboring Trypanosomatids (SHTs) and not in the bacteria. The bacterium has specific sequences and genes related to phosphatidylglycerol and phosphatidic acid production, which likely enhance SHT phosphatidic acid production. Phylogenetic analysis suggests that enzymes involved in the glycerophospholipid pathway have eukaryotic characteristics, indicating no gene transfers from the bacterium to the SHT nucleus. Overall, the data indicate that the symbiont plays a limited role in glycerophospholipid production, acquiring most of these molecules from the SHT.
Article
Cell Biology
Juliana C. Vidal, Wanderley De Souza
Summary: In this study, we used FIB-SEM to analyze the three-dimensional organization of epimastigotes SPMT and found that certain microtubules end earlier than their neighboring ones. This suggests the presence of treadmill/catastrophe events that have not yet been described in trypanosomatids.
BIOLOGY OF THE CELL
(2022)
Article
Microbiology
Luana P. Borba-Santos, Caroline Deckmann Nicoletti, Taissa Vila, Patricia Garcia Ferreira, Carlos Fernando Araujo-Lima, Barbara Verena Dias Galvao, Israel Felzenszwalb, Wanderley de Souza, Fernando de Carvalho da Silva, Vitor Francisco Ferreira, Debora Omena Futuro, Sonia Rozental
Summary: The silver salt of naphthoquinone 5 was found to possess potent antifungal activity against the main agents of sporotrichosis, inhibiting biofilm formation and causing mitochondrial and plasma membrane damage in fungal cells. Combination with itraconazole enhanced its inhibitory activity, and it showed a high selectivity towards fungal cells. These findings suggest that naphthoquinone 5 is a promising candidate for the development of new antifungal agents.
BRAZILIAN JOURNAL OF MICROBIOLOGY
(2022)
Article
Parasitology
Duclecio Mendonca Lopes, Aluizio Fonseca Provencano, Cicero Brasileiro Mello, Denise Feder, Jose Mauricio Albuquerque Albuquerque Cunha, Nadir Francisca Sant'Anna, Guilherme Curty Lechuga, Saulo Cabral Bourguignon, Wanderley de Souza, Eloi de Souza Garcia, Evelize Folly, Patricia Azambuja, Marcelo Salabert Gonzalez
Summary: This study investigated the effects of azadirachtin treatment, ecdysone supplementation, and ecdysone therapy on the ultrastructural organization of the rectum in Rhodnius prolixus nymphs and the attachment behavior of Trypanosoma cruzi. The results suggest that ecdysone may play a significant role in the modulation of rectal ultrastructural arrangement and parasite attachment.
EXPERIMENTAL PARASITOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jarlene A. Lopes, Federica Collino, Clara Rodrigues-Ferreira, Luzia da Silva Sampaio, Gloria Costa-Sarmento, Camila H. C. Wendt, Fernando P. Almeida, Kildare R. Miranda, Tais H. Kasai-Brunswick, Rafael S. Lindoso, Adalberto Vieyra
Summary: This study investigated whether extracellular vesicles secreted by adipose tissue mesenchymal cells (EVs) can suppress the excessive production of mitochondrial O-2(center dot-) caused by acute kidney injury (AKI). The results showed that administration of EVs can decrease mitochondrial O-2(center dot-) formation and promote the recovery of renal structures and functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Luana Pereira Borba-Santos, Rodrigo Rollin-Pinheiro, Yasmin da Silva Fontes, Giulia Maria Pires dos Santos, Glauber Ribeiro de Sousa Araujo, Anderson Messias Rodrigues, Allan J. Guimaraes, Wanderley de Souza, Susana Frases, Antonio Ferreira-Pereira, Eliana Barreto-Bergter, Sonia Rozental
Summary: High-content screening of compounds from the Pandemic Response Box library identified olorofim as a promising new antifungal drug against Sporothrix pathogenic species. Olorofim showed inhibitory and lethal effects on several Sporothrix species at lower concentrations than itraconazole, and it also displayed antibiofilm activity. The drug induced significant alterations on the cell surface and cell cycle arrest in Sporothrix yeasts, impairing their ability to adhere to keratinocytes.
Article
Biochemistry & Molecular Biology
Cassiano Cunha de Souza, Jose Aleixo de Azevedo-Franca, Emile Barrias, Stephany C. F. Cavalcante, Eduardo Guimaraes Vieira, Ana Maria Da Costa Ferreira, Wanderley de Souza, Maribel Navarro
Summary: Four novel metal-BZN complexes were synthesized and characterized in this study. The IC50 values of these complexes in inhibiting parasite proliferation stages are five to ten times lower than benznidazole itself. The cytotoxicity in human cells is lower for these complexes compared to BZN, indicating higher selectivity.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Aline Araujo Zuma, Wanderley de Souza
Summary: Fexinidazole has been found to have potential against Trypanosoma cruzi, the causative agent of Chagas disease. It can inhibit parasite proliferation and cause significant alterations in cellular structures.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Wendell Girard-Dias, Ingrid Augusto, Tacio V. A. Fernandes, Pedro G. Pascutti, Wanderley de Souza, Kildare Miranda
Summary: In this study, the three-dimensional distribution of diffusible elements within acidocalcisomes in Trypanosoma cruzi was mapped using advanced electron microscopy techniques. The existence of nanodomains with specific element distribution patterns was discovered. These findings have significant implications for understanding nanophysiology of organelles.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Anna L. S. Barreto, Ariadne N. Alonso, Daniel C. De Moraes, Jose A. R. Curvelo, Kildare Miranda, Maristela B. Portela, Antonio Ferreira-Pereira, Thais Souto-Padron, Rosangela Maria De A. Soares
Summary: The search for new therapeutic strategies for leishmaniasis treatment is essential. The aqueous extract of the marine sponge Dercitus (Stoeba) latex displayed antileishmanial activity and moderate toxicity against peritonial macrophages. This study suggests that Dercitus (Stoeba) latex may be a potential source of drugs for the treatment of L. amazonensis infections.
ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS
(2022)
Article
Nanoscience & Nanotechnology
Jhon Jhamilton Artunduaga Bonilla, Leandro Honorato, Allan J. Guimaraes, Kildare Miranda, Leonardo Nimrichter
Summary: This research focuses on the green synthesis of chitosan-functionalized silver nanoparticles (AgNPs@Chi) and their potential applications in combating sporotrichosis. The results demonstrate that AgNPs@Chi exhibit low toxicity, inhibitory effects on fungal growth, and stimulating effects on cell growth and tissue repair. These nanocomposites have the potential to be a non-toxic and efficient alternative for sporotrichosis treatment.
FRONTIERS IN NANOTECHNOLOGY
(2022)