Article
Cell Biology
Noelie Douanne, George Dong, Atia Amin, Lorena Bernardo, Mathieu Blanchette, David Langlais, Martin Olivier, Christopher Fernandez-Prada
Summary: This study investigates the DNA content of Leishmania extracellular vesicles (EVs) and their role in DNA transfer. It is found that drug-resistant EVs carry amplicons associated with drug-resistance genes. Transfer experiments demonstrate that the transferred DNA significantly impacts the phenotype of recipient parasites, enhancing their growth and ability to withstand oxidative stress. These findings provide evidence for the important role of eukaryotic EVs in horizontal gene transfer and adaptation to stressful environments.
Article
Immunology
Paulo R. L. Machado, Fernanda V. O. Prates, Viviane Boaventura, Taina Lago, Luiz H. Guimaraes, Albert Schriefer, Temis W. F. Corte, Gerson Penna, Aldina Barral, Manoel Barral-Netto, Edgar M. Carvalho
Summary: The study showed that miltefosine is more effective than pentavalent antimony for treating cutaneous leishmaniasis caused by L. braziliensis in Brazil, and it accelerates healing time. However, combining miltefosine with GM-CSF did not improve therapeutic outcome but did shorten the healing time.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Medicine, General & Internal
Juliana B. T. Carnielli, Anuja Dave, Audrey Romano, Sarah Forrester, Pedro R. de Faria, Renata Monti-Rocha, Carlos H. N. Costa, Reynaldo Dietze, Ian A. Graham, Jeremy C. Mottram
Summary: In Brazil, miltefosine treatment failure in visceral leishmaniasis has been linked to the deletion of the miltefosine susceptibility locus (MSL) in Leishmania infantum. CRISPR-Cas9 was used to investigate the role of NUC1, NUC2, HLP, and TEI in miltefosine resistance mechanisms. Findings suggest that the absence of NUC1 and NUC2 from the MSL contributes to natural resistance to miltefosine in L. infantum.
Article
Chemistry, Medicinal
Caroline R. Espada, Andreia Albuquerque-Wendt, Valentin Hornillos, Eva Gluenz, Adriano C. Coelho, Silvia R. B. Uliana
Summary: The ros3 gene copy number was found to be associated with increased miltefosine uptake and susceptibility in Leishmania. Modulating the gene copy number showed significant impact on miltefosine susceptibility, with overexpression leading to increased EC50 values and deletion resulting in higher EC50 values. This study confirms that ros3 copy number is a factor affecting differential susceptibility and uptake of miltefosine.
ACS INFECTIOUS DISEASES
(2021)
Article
Microbiology
Sneider Alexander Gutierrez Guarnizo, Elena B. Tikhonova, Masoud Zabet-Moghaddam, Kai Zhang, Carlos Muskus, Andrey L. Karamyshev, Zemfira N. Karamysheva
Summary: The study used lipidomic profiles to differentiate between sensitive and resistant Leishmania strains, showing that resistant phenotypes had downregulated phosphatidylcholines, decreased sphingolipids, and increased lysophosphatidylcholines, while sensitive phenotypes had upregulated triglycerides and decreased phosphatidylethanolamine. The changes in lipid composition in antimony-resistant parasites appear to contribute to their physiological response to combat oxidative stress caused by the drug, highlighting several lipids as potential biomarkers for drug resistance.
Article
Chemistry, Organic
Ayelen Luczywo, Ismael Pretto Sauter, Thalita Camelo da Silva Ferreira, Mauro Cortez, Gustavo P. Romanelli, Gabriel Sathicq, Silvia E. Asis
Summary: A series of 2-styryl-4-quinolinecarboxylic acids were synthesized under microwave irradiation settings, showing promising antileishmanial activity against intracellular parasites. Compounds 4 and 5, with 2-chloro or 4-chlorostyryl moieties, were considered the most hopeful agents due to their significant parasite killing effect inside infected macrophages.
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2021)
Article
Parasitology
Chonlada Mano, Aphisek Kongkaew, Pongsri Tippawangkosol, Anuluck Junkum, Padet Siriyasatien, Narissara Jariyapan
Summary: This study reveals the resistance of Leishmania martiniquensis to amphotericin B deoxycholate (AmpB) and miltefosine (MIL), and suggests further research into the mechanisms of this resistance and the development of effective methods to identify drug-resistant parasites.
PARASITOLOGY RESEARCH
(2023)
Article
Infectious Diseases
Ankita Rani, Shilpika Khanikar, Mukul Dutta, Shivani Katiyar, Tooba Qamar, Anuradha Seth, P. K. Agnihotri, Rajdeep Guha, Jai N. Vishwakarma, Susanta Kar
Summary: Compound 3D-mediated inhibition of L. donovani mitochondrial complex induces apoptosis, showing potential therapeutic activity against visceral leishmaniasis.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Microbiology
Caroline Ricce Espada, Erica V. de Castro Levatti, Mariana Cortes Boite, Dorcas Lamounier, Jorge Alvar, Elisa Cupolillo, Carlos Henrique Nery Costa, Joelle Rode, Silvia R. B. Uliana
Summary: This study investigated the susceptibility of 73 Brazilian strains of Leishmania infantum to miltefosine, showing relatively low heterogeneity in miltefosine susceptibility. The results suggest that Brazilian L. infantum may not have decreased susceptibility to miltefosine, indicating the potential for future clinical evaluation of miltefosine for VL treatment in Brazil.
Article
Biochemistry & Molecular Biology
Chung-Pu Wu, Yen-Ching Li, Megumi Murakami, Sung-Han Hsiao, Yun-Chieh Lee, Yang-Hui Huang, Yu-Tzu Chang, Tai-Ho Hung, Yu-Shan Wu, Suresh V. Ambudkar
Summary: This study aims to evaluate whether furmonertinib overcomes drug resistance mediated by ABCB1 and ABCG2 transporters, and explore its interaction mechanisms with these proteins. The results suggest that furmonertinib holds potential as a candidate for combination therapy, enhancing the efficacy of conventional anticancer drugs and overcoming MDR in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Chung-Pu Wu, Sung-Han Hsiao, Yu-Shan Wu
Summary: The overexpression of human ATP-binding cassette (ABC) transporters in cancer cells can lead to multidrug resistance (MDR), which poses a significant obstacle to chemotherapy. Currently, there are no approved drugs specifically designed to treat multidrug-resistant cancers. However, drug repurposing has emerged as a practical approach to discover effective modulators of drug transporters.
DRUG RESISTANCE UPDATES
(2023)
Article
Oncology
Kosuke Tanaka, Helena A. Yu, Shaoyuan Yang, Song Han, S. Duygu Selcuklu, Kwanghee Kim, Shriram Ramani, Yogesh Tengarai Ganesan, Allison Moyer, Sonali Sinha, Yuchen Xie, Kota Ishizawa, Hatice U. Osmanbeyoglu, Yang Lyu, Nitin Roper, Udayan Guha, Charles M. Rudin, Mark G. Kris, James J. Hsieh, Emily H. Cheng
Summary: Combination therapy with EGFR and Aurora B inhibitors enhances osimertinib-induced apoptosis, effectively eliminating cancer cells and overcoming resistance, mainly by affecting the stability of BIM and PUMA.
Article
Biochemistry & Molecular Biology
Jianyi Li, Yuntong Lv, Kunpeng Yan, Fengting Yang, Xuewei Chen, Xiwu Gao, Shuyuan Wen, Hongfei Xu, Yiou Pan, Qingli Shang
Summary: The study revealed that ATP-binding cassette transporters (ABCs) play important roles in cyantraniliprole resistance. Inhibition of ABCs increased the toxicity of cyantraniliprole, while overexpression of ABCs in fruit flies enhanced their tolerance to cyantraniliprole. Suppression of specific ABC transporters increased the sensitivity of cyantraniliprole-resistant strains. These findings provide valuable insights for resistance management strategies.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Wei-liang Qi, Hui-yu Li, Yi Wang, Lan Xu, Jie-ting Deng, Xi Zhang, Yu-xiang Wang, Ling-hua Meng
Summary: This study identified the mechanism of acquired resistance to KRas(G12C) inhibitors and suggested that simultaneous inhibition of EGFR and IGF1R can restore drug sensitivity. The level of PI3K activation is negatively correlated with the anti-proliferative activity of AMG510, and concurrent treatment with the PI3K alpha inhibitor CYH33 exhibits a synergistic effect.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Budhaditya Mukherjee, Kamalika Mukherjee, Piyush Nanda, Rupkatha Mukhopadhayay, V. Ravichandiran, Suvendra N. Bhattacharyya, Syamal Roy
Summary: Visceral leishmaniasis caused by Leishmania donovani can develop resistance to pentavalent antimonial drugs, leading to more aggressive infection in mammals. Alterations in miRNA pathways may provide a new strategy to control infection caused by drug-resistant parasites.
Article
Biochemistry & Molecular Biology
Ruben Perandres-Lopez, Maria P. Sanchez-Canete, Francisco Gamarro, Santiago Castanys
BIOCHEMICAL JOURNAL
(2018)
Article
Chemistry, Medicinal
Efres Belmonte-Reche, Marta Martinez-Garcia, Aurore Guedin, Michela Zuffo, Matilde Arevalo-Ruiz, Filippo Doria, Jenny Campos-Salinas, Marjorie Maynadier, Jose Juan Lopez-Rubio, Mauro Freccero, Jean-Louis Mergny, Jose Maria Perez-Victoria, Juan Carlos Morales
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Parasitology
Marta Martinez-Garcia, Jean-Mathieu Bart, Jenny Campos-Salinas, Eva Valdivia, Manuel Martinez-Bueno, Elena Gonzalez-Rey, Miguel Navarro, Mercedes Maqueda, Ruben Cebrian, Jose M. Perez-Victoria
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2018)
Article
Parasitology
Alberto Rastrojo, Raquel Garcia-Hernandez, Paola Vargas, Esther Camacho, Laura Corvo, Hideo Imamura, Jean-Claude Dujardin, Santiago Castanys, Begona Aguado, Francisco Gamarro, Jose M. Requena
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2018)
Article
Plant Sciences
Ignacio Fernandez-Pastor, Marta Martinez-Garcia, Marta Medina-O'Donnell, Francisco Rivas, Antonio Martinez, Jos Maria Perez-Victoria, Andres Parra
JOURNAL OF NATURAL PRODUCTS
(2018)
Article
Biochemical Research Methods
Eduardo Mayol, Mercedes Campillo, Arnau Cordomi, Mireia Olivella
Article
Chemistry, Medicinal
M. Zuffo, A. Stucchi, J. Campos-Salinas, M. Cabello-Donayre, M. Martinez-Garcia, E. Belmonte-Reche, J. M. Perez-Victoria, J. L. Mergny, M. Freccero, J. C. Morales, F. Doria
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Maria Cabello-Donayre, Lina M. Orrego, Elisa Herraez, Paola Vargas, Marta Martinez-Garcia, Jenny Campos-Salinas, Ignacio Perez-Victoria, Belen Vicente, Jose J. G. Marin, Jose M. Perez-Victoria
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Lina M. Orrego, Maria Cabello-Donayre, Paola Vargas, Marta Martinez-Garcia, Clara Sanchez, Estela Pineda-Molina, Maribel Jimenez, Ricardo Molina, Jose M. Perez-Victoria
Article
Biochemistry & Molecular Biology
J. Perner, T. Hatalova, M. Cabello-Donayre, V. Urbanova, D. Sojka, H. Frantova, D. Hartmann, D. Jirsova, J. M. Perez-Victoria, P. Kopacek
Summary: Ticks have lost genes encoding haem biosynthetic enzymes, making them dependent on acquiring host haem. The haem transporter IrHRG has been identified in ticks, facilitating the transport of haemoglobin-derived haem for usage in a haem-dependent enzyme network. This highlights the importance of retaining the hrg1 gene in ticks for evolutionary survival.
Article
Biochemistry & Molecular Biology
Ruben Cebrian, Ricardo Lucas, Maria Victoria Fernandez-Cantos, Koen Slot, Pablo Penalver, Marta Martinez-Garcia, Antonio Parraga-Leo, Maria Violante de Paz, Federico Garcia, Oscar P. P. Kuipers, Juan Carlos Morales
Summary: In this study, a family of aminoalkyl resveratrol derivatives with antibacterial activity inspired by cationic amphipathic antimicrobial peptides was discovered. These molecules showed good antimicrobial activity against anaerobic bacteria and exhibited synergistic effects with traditional antibiotics against Gram-negative pathogens. The mechanism of action was found to be at the membrane level and no cross-resistance was observed, although some cytotoxicity was detected.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Review
Microbiology
Ruben Cebrian, Marta Martinez-Garcia, Matilde Fernandez, Federico Garcia, Manuel Martinez-Bueno, Eva Valdivia, Oscar. P. P. Kuipers, Manuel Montalban-Lopez, Mercedes Maqueda
Summary: Antimicrobial resistance is a serious threat to global public health and economy. Antimicrobial peptides, such as AS-48, offer a promising solution due to their unique mechanisms of action and stability. AS-48 has demonstrated potential against a wide range of pathogens and could be a valuable tool in the fight against antimicrobial resistance.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria Cabello-Donayre, Lina M. Orrego, Elisa Herraez, Raquel Garcia-Hernandez, Jose M. Perez-Victoria
Summary: This study investigated the uptake of heme in Leishmania parasites, finding that it is an active, inducible, and pH-dependent process that does not require a plasma membrane proton gradient but requires the presence of Na+ and/or K+. The researchers also discovered differences in heme uptake among different Leishmania species and showed that the involved transporters have partially overlapping functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ana Perea, Jose Ignacio Manzano, Yasuhisa Kimura, Kazumitsu Ueda, Santiago Castanys, Francisco Gamarro
BIOCHEMICAL JOURNAL
(2018)