Article
Microbiology
Raquel Garcia-Hernandez, Ana Perea-Martinez, Jose Ignacio Manzano, Laura C. Terron-Camero, Eduardo Andres-Leon, Francisco Gamarro
Summary: Leishmaniasis, a neglected tropical disease, lacks an effective vaccine and drug resistance as well as therapeutic failure are major challenges for treatment. This study found significant changes in gene expression in Leishmania parasites isolated from patients with therapeutic failure. These changes may improve the survival of the parasites in host cells, contributing to therapeutic failure.
Article
Immunology
Graziele Quintela-Carvalho, Astrid Madeleine Calero Goicochea, Vanessa Mancur-Santos, Sayonara de Melo Viana, Yasmin da Silva Luz, Beatriz Rocha Simoes Dias, Milena Lazaro-Souza, Martha Suarez, Camila Indiani de Oliveira, Elvira M. Saraiva, Claudia Brodskyn, Patricia T. Veras, Juliana P. B. de Menezes, Bruno B. Andrade, Jonilson Berlink Lima, Albert Descoteaux, Valeria M. Borges
Summary: Lipophosphoglycan (LPG) may play a critical role in promoting Leishmania survival in human neutrophils through cellular activation and generation of free radicals, thereby influencing the process of infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kendi Okuda, Miriam Maria Silva Costa Franco, Ari Yasunaga, Ricardo Gazzinelli, Michel Rabinovitch, Sara Cherry, Neal Silverman
Summary: Leishmania parasites utilize virulence mechanisms to invade and replicate in macrophages, inhibiting host defenses and altering gene expression to enhance their survival and replication.
Article
Multidisciplinary Sciences
Greta Volpedo, Thalia Pacheco-Fernandez, Timur Gannavaram, Hannah L. Markle, Nazli Azodi, Shinjiro Hamano, Greg Matlashewski, Sreenivas Gannavaram, Hira L. Nakhasi, Abhay R. Satoskar
Summary: Leishmaniasis is a prevalent tropical disease for which there is currently no approved human vaccine. In this study, a live attenuated L. mexicana strain was developed and shown to induce a strong immune response in mice. The research also revealed the important role of the pentose phosphate pathway in the immune mechanism of protection.
Article
Microbiology
Mayra M. Reimann, Eduardo Caio Torres-Santos, Celeste S. F. de Souza, Valter V. Andrade-Neto, Ana Maria Jansen, Reginaldo P. Brazil, Andre Luiz R. Roque
Summary: This study demonstrates that Leishmania parasites can infect hosts through oral and intragastric routes, which is crucial for understanding their transmission dynamics in nature.
Article
Immunology
Susanne U. Franssen, Mandy J. Sanders, Matt Berriman, Christine A. Petersen, James A. Cotton
Summary: This study presents genomic data from Leishmania-infected dogs in the United States, demonstrating vertical transmission of the parasites without vector transmission. The parasites were introduced to the US separately from the Old World and more recently than L. infantum from South America. The unusual genetics of the parasite population suggest limited or no sexual reproduction. The findings have important implications for the population genetics of Leishmania parasites and highlight the need to consider vertical transmission in addition to vector transmission when studying transmission in complex natural settings.
EMERGING INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Yosser Zina Abdelkrim, Emna Harigua-Souiai, Imen Bassoumi-Jamoussi, Mourad Barhoumi, Josette Banroques, Khadija Essafi-Benkhadir, Michael Nilges, Arnaud Blondel, N. Kyle Tanner, Ikram Guizani
Summary: This study investigated the mode of action of cholesterol derivatives as novel LieIF4A inhibitors and found that 7-alpha-aminocholesterol has a higher binding affinity and inhibitory effect on Leishmania.
Article
Immunology
Jaime Larraga, Pedro J. Alcolea, Ana M. Alonso, Luis T. C. Martins, Inmaculada Moreno, Mercedes Dominguez, Vicente Larraga
Summary: Leishmania parasites cause significant morbidity and mortality in many developing countries. Researchers have identified a vaccine candidate, LiUBC1, which shows partial protection against L. infantum infection in a Syrian hamster model.
Article
Parasitology
Geovane Dias-Lopes, Anabel Zabala-Penafiel, Barbara Cristina de Albuquerque-Melo, Franklin Souza-Silva, Laura Menaguali do Canto, Lea Cysne-Finkelstein, Carlos Roberto Alves
Summary: Leishmania spp. can be fatal and their main forms, promastigotes and amastigotes, can be maintained in vitro. Differentiation from promastigotes to axenic amastigotes has been proposed, but a consensus on inducing parameters and biomarkers is needed for better accuracy.
Article
Agriculture, Dairy & Animal Science
Maria Edo, Pablo Jesus Marin-Garcia, Lola Llobat
Summary: Leishmaniosis is an important zoonotic protozoan disease primarily spread to the Mediterranean region by Leishmania infantum, the predominant protozoan species. The study analyzed the prevalence of infection in different dog breeds from Ibizan Island and found a higher prevalence in Doberman Pinschers and Boxers, confirming a relationship between antibody serum titer and disease staging.
Article
Parasitology
Ana Isabel Olias-Molero, Pedro Botias, Montserrat Cuquerella, Jesus Garcia-Cantalejo, Emilia Barcia, Susana Torrado, Juan Jose Torrado, Jose Maria Alunda
Summary: The study in Syrian hamsters infected with L. infantum found no significant changes in intestinal microbiome composition after infection, suggesting a lack of clear relationship between VL infection and intestinal microbiome composition in hamsters.
PARASITES & VECTORS
(2022)
Article
Parasitology
Ana Maria Murta Santi, Paula Alves Silva, Isabella Fernandes Martins Santos, Silvane Maria Fonseca Murta
Summary: FeSOD-A is essential in L. infantum and plays a crucial role in defense against oxidative stress and infectivity. FeSOD-A-deficient parasites deregulate metabolic pathways related to antimony and miltefosine resistance.
PARASITES & VECTORS
(2021)
Article
Microbiology
Valter V. Andrade-Neto, Karina M. Rebello, Thais M. Pereira, Eduardo Caio Torres-Santos
Summary: This study evaluated the efficacy of a ternary therapy composed of itraconazole, ezetimibe, and miltefosine for the treatment of visceral leishmaniasis, demonstrating synergistic effects in intracellular amastigotes. The results showed promising outcomes for low-dose ternary treatment, indicating it as a potential therapeutic alternative for visceral leishmaniasis.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Chemistry, Multidisciplinary
Crhisllane Rafaele dos Santos Vasconcelos, Antonio Mauro Rezende
Summary: Leishmaniasis, a neglected infectious disease, was studied using computational methods to evaluate potential drug targets in the predicted proteomes of Leishmania braziliensis and Leishmania infantum, revealing several untested proteins with potential therapeutic value.
FRONTIERS IN CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Pasquale Rombola, Giulia Barlozzari, Andrea Carvelli, Manuela Scarpulla, Francesca Iacoponi, Gladia Macri
Summary: Canine leishmaniasis is a zoonotic parasitic disease endemic in the Mediterranean area, with domestic dogs as the main reservoir host. This study in the Lazio region of central Italy assessed the seroprevalence and identified factors influencing the exposure of dogs to Leishmania infantum.
Article
Chemistry, Medicinal
Solida Long, Denise Duarte, Carla Carvalho, Rafael Oliveira, Nuno Santarem, Andreia Palmeira, Diana I. S. P. Resende, Artur M. S. Silva, Rui Moreira, Anake Kijjoa, Anabela Cordeiro da Silva, Fatima Nogueira, Emilia Sousa, Madalena M. M. Pinto
Summary: The study explored the antiparasitic potential of pyrazino [2,1-6] quinazoline-3,6-diones containing indole alkaloids against Plasmodium falciparum, Trypanosoma brucei, and Leishmania infantum. Promising hit compounds with species-specific or broad antiparasitic activity were identified, and structure-activity relationships were observed. In silico studies predicted these compounds as possible inhibitors for prolyl-tRNA synthetase both from Plasmodium and Leishmania, indicating their potential for the development of novel and affordable antiparasitic drugs.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Monica Sa, David Mendes Costa, Ana Rafaela Teixeira, Begona Perez-Cabezas, Pauline Formaglio, Sylvain Golba, Helena Sefiane-Djemaoune, Rogerio Amino, Joana Tavares
Summary: This study investigated the importance of the membrane-associated erythrocyte binding-like protein (MAEBL) in Plasmodium sporozoite infection, showing that its absence reduces infectivity in mice and affects adhesion to hepatocytes. The findings suggest a potential role for MAEBL in immune intervention strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
J. G. B. De Marchi, R. Ce, G. Onzi, A. C. S. Alves, N. Santarem, A. Cordeiro da Silva, A. R. Pohlmann, S. S. Guterres, A. J. Ribeiro
Summary: This study aims to improve the absorption of nanoparticle formulation by functionalizing its surface with immunoglobulin G. The functionalized nanoparticles showed adequate size and good entrapment efficiency, and led to a desirable increase in insulin release time. Interactions of nanoparticle components were proven through differential scanning calorimetry, infrared spectroscopy, and paper chromatography.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Review
Immunology
Valeria Aoki, Maha Abdeladhim, Ning Li, Pedro Cecilio, Phillip Prisayanh, Luis A. A. Diaz, Jesus G. G. Valenzuela
Summary: Sand flies are blood-sucking insects that transmit vector-borne diseases to humans. Their saliva contains pharmacologically active components that aid in blood-feeding and pathogen establishment. Sand fly salivary proteins have potential uses as biomarkers of vector exposure or as anti-Leishmania vaccines. However, some of these proteins can trigger the formation of cross-reactive antibodies that are associated with autoimmune skin diseases in certain individuals.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Ana Rafaela Teixeira, Begona Perez-Cabezas, David M. Costa, Monica Sa, Sylvain Golba, Helena Sefiane-Djemaoune, Joana Ribeiro, Izumi Kaneko, Shiroh Iwanaga, Masao Yuda, Moriya Tsuji, Silvia Beatriz Boscardin, Rogerio Amino, Anabela Cordeiro-da-Silva, Joana Tavares
Summary: This study demonstrates that using 5'ppp-dsRNA as an adjuvant to CSP vaccines can induce effective anti-Plasmodium humoral immunity. The vaccine generates high levels of functional antibodies, which can target and kill the sporozoites, providing early and long-lasting sterile protection against both stringent sporozoite and mosquito bite challenges. The use of poly(A:U) as an adjuvant, on the other hand, results in high antibody levels but less functional antibodies and therefore less protection.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biology
Pedro Cecilio, Anabela Cordeiro-da-Silva, Fabiano Oliveira
Summary: This review discusses various aspects of sand flies as vectors of Leishmania parasites, including their basic biology, ecology, and interactions with the parasites. It highlights the need to study the vectors as well as the diseases and etiological agents.
COMMUNICATIONS BIOLOGY
(2022)
Article
Chemistry, Medicinal
Ina Poehner, Antonio Quotadamo, Joanna Panecka-Hofman, Rosaria Luciani, Matteo Santucci, Pasquale Linciano, Giacomo Landi, Flavio Di Pisa, Lucia Dello Iacono, Cecilia Pozzi, Stefano Mangani, Sheraz Gul, Gesa Witt, Bernhard Ellinger, Maria Kuzikov, Nuno Santarem, Anabela Cordeiro-da-Silva, Maria P. Costi, Alberto Venturelli, Rebecca C. Wade
Summary: This study presents a systematic, multidisciplinary approach to the development of selective antiparasitic compounds with multiple targets. The approach combines computational fragment-based design and crystallographic structure determination to derive a structure-activity relationship for multitarget inhibition. The optimized compounds show promising inhibition against various parasitic targets while minimizing toxicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Andre Lopes, Nuno Santarem, Anabela Cordeiro-da-Silva, M. Alice Carvalho
Summary: In this study, new pyrimido[5,4-d]pyrimidines were designed, synthesized, and evaluated for their activity against Trypanosoma brucei and Leishmania infantum in vitro. One compound showed activity against both parasites, indicating the potential for developing novel antitrypanosomal and antileishmanial agents.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Microbiology
Alberto Venturelli, Lorenzo Tagliazucchi, Clara Lima, Federica Venuti, Giulia Malpezzi, George E. Magoulas, Nuno Santarem, Theodora Calogeropoulou, Anabela Cordeiro-da-Silva, Maria Paola Costi
Summary: Human African Trypanosomiasis (HAT) and Animal African Trypanosomiasis (AAT) are tropical diseases caused by the same pathogen. Despite progress in controlling HAT, AAT remains a reservoir of infection. Clearer guidelines are needed to address the challenges of drug use and resistance development.
Article
Microbiology
Carla Silva Lima, Sofia Esteves, Ines Costa, Hugo Brancal, Clara Lima, Celia Amorim, Luis Cardoso, Nuno Santarem, Anabela Cordeiro-da-Silva
Summary: Canine leishmaniosis is a disease caused by Leishmania infantum in dogs, which can result in non-specific clinical signs or a subclinical condition. This study evaluated the impact of using different antigens in a serological survey and proposed a serological score system to address complex serology results.
Article
Biochemistry & Molecular Biology
Sofia Esteves, Clara Lima, Ines Costa, Hugo Osorio, Carmen Fernandez-Becerra, Nuno Santarem, Anabela Cordeiro-da-Silva
Summary: Dogs are susceptible to many life-threatening conditions like Canine Leishmaniosis (CanL), making it important to identify proteins associated with plasma extracellular vesicles (EVs) for biomarker development. In this study, EVs were recovered from healthy and CanL dogs' plasma and analyzed for their proteomic composition. CanL-associated proteins were identified, providing insights for biomarker discovery.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Microbiology
Nuno Santarem, Luis Cardoso, Anabela Cordeiro-da-Silva
Article
Chemistry, Medicinal
Ina Poehner, Antonio Quotadamo, Joanna Panecka-Hofman, Rosaria Luciani, Matteo Santucci, Pasquale Linciano, Giacomo Landi, Flavio Di Pisa, Lucia Dello Iacono, Cecilia Pozzi, Stefano Mangani, Sheraz Gul, Gesa Witt, Bernhard Ellinger, Maria Kuzikov, Nuno Santarem, Anabela Cordeiro-da-Silva, Maria P. Costi, Alberto Venturelli, Rebecca C. Wade
Summary: In this study, a systematic and multidisciplinary approach was used to develop selective antiparasitic compounds. Through computational fragment-based design and crystallographic structure determination, compounds with activity against multiple targets were obtained. Additionally, the combination of polypharmacology design and parasite-specific optimization led to the discovery of compounds effective against T. brucei brucei.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)