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
Infectious Diseases
Bianca A. Ferreira, Gustavo de A. Santos, Elizabeth M. Coser, Juliana M. Sousa, Monica E. A. Gama, Leonidas L. B. Junior, Fabricio S. Pessoa, Mayara I. S. Lima, Silvia R. B. Uliana, Adriano C. Coelho
Summary: This study isolated a species of Leishmania parasite from a pediatric patient with visceral leishmaniasis and found that the patient did not respond to chemotherapy. In vitro susceptibility assays showed that the parasite was sensitive to all the drugs currently used in the chemotherapy of leishmaniasis.
TROPICAL MEDICINE AND INFECTIOUS DISEASE
(2023)
Article
Parasitology
Elizabeth M. Coser, Bianca A. Ferreira, Edite H. Yamashiro-Kanashiro, Jose Angelo L. Lindoso, Adriano C. Coelho
Summary: Treatment of tegumentary leishmaniasis in Brazil is currently limited to a few drugs, highlighting the need for expansion of therapeutic options. Paromomycin, an aminoglycoside antibiotic already approved for visceral leishmaniasis, shows promising activity against clinical isolates of tegumentary leishmaniasis in Brazil.
Review
Parasitology
Taylon Felipe Silva, Fernanda Tomiotto-Pellissier, Aline Kuhn Sbruzzi Pasquali, Fernanda Pinto-Ferreira, Wander Rogerio Pavanelli, Ivete Conchon-Costa, Italmar Teodorico Navarro, Eloiza Teles Caldart
Summary: The study revealed that the exact mechanism leading to different clinical manifestations among strains of the same species is still uncertain, and future studies are needed to better elucidate this phenomenon.
Article
Agriculture, Dairy & Animal Science
Zhiwan Zheng, Jinlei He, Tao Luo, Jianhui Zhang, Qi Zhou, Shuangshuang Yin, Dali Chen, Jie Luo, Jianping Chen, Jiao Li
Summary: Leishmaniasis is a neglected tropical disease that threatens millions of people worldwide. The emergence of antimony-resistant Leishmania strains has posed challenges to the treatment and elimination of leishmaniasis. In this study, genome sequencing, phylogenetic analysis, and mutation analysis were performed on five clinical isolates of Leishmania, with a focus on the newly isolated L_HCZ strain in 2016, which showed strong virulence and antimony resistance.
Article
Microbiology
Jack D. Sobel, Robert Akins
Summary: Antifungal drug susceptibility tests (AST) are increasingly needed for women with refractory or recurrent Candida vaginitis due to fluconazole resistance. It is proposed that the AST be performed at pH 4.5 instead of the recommended pH 7.0, as testing at only pH 7.0 is likely to miss a significant number of clinically relevant azole-resistant C. albicans vaginal isolates.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Parasitology
Bianca A. Ferreira, Thaynan F. C. Martins, Elizabeth M. Coser, Viviane da L. Oliveira, Edite H. Yamashiro-Kanashiro, Mussya C. Rocha, Marcelo M. Pinto, Paulo C. Cotrim, Adriano C. Coelho
Summary: The study confirmed the endemicity of canine leishmaniasis in Embu das Artes, Brazil, and found that isolates from this region are susceptible to paromomycin and miltefosine, indicating the potential of these drugs for the clinical treatment of human visceral leishmaniasis in Brazil.
PARASITOLOGY RESEARCH
(2022)
Article
Microbiology
Helena Fehling, Hanno Niss, Annika Bea, Nadine Kottmayr, Christine Brinker, Stefan Hoenow, Julie Sellau, Tim-Wolf Gilberger, Frederic Ting, Dirk Landschulze, Chris Meier, Joachim Clos, Hannelore Lotter
Summary: A study introduced an immunostimulatory glycolipid molecule from the intestinal protozoan parasite Entamoeba histolytica (Eh) and its synthetic analogs for potential immunotherapeutic effects against Leishmania major infection. Using a screening assay based on primary murine macrophages, the research demonstrated the potential of six immunostimulatory EhPIb-compounds for treating cutaneous and visceral leishmaniasis, with compound Eh-6 exhibiting activity against all Leishmania species.
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
Adam J. Roberts, Han B. Ong, Simon Clare, Cordelia Brandt, Katherine Harcourt, Susanne U. Franssen, James A. Cotton, Nicole Mueller-Sienerth, Gavin J. Wright
Summary: This study aims to discover essential proteins for in vitro growth and host infection of Leishmania spp., with the goal of identifying subunit vaccine candidates. Through in silico analysis and genome editing, potential subunit vaccine candidates have been identified. Preclinical trials in a murine model showed significant levels of protection against splenic infection.
Article
Microbiology
Ming Wei, Xinmin Xu, Jingxian Yang, Peng Wang, Yongzhe Liu, Shuai Wang, Chunxia Yang, Li Gu
Summary: This study analyzed the species distribution and drug susceptibility of 82 clinical Nocardia isolates from three tertiary hospitals in China. Pulmonary nocardiosis was the most common clinical presentation, and trimethoprim/sulfamethoxazole remained highly active against all isolates. High resistance rates were observed for clarithromycin and ciprofloxacin, but N. farcinica showed low resistance to ciprofloxacin.
Review
Pharmacology & Pharmacy
Chun-Ka Wong, Hung-Fat Tse
Summary: Atrial fibrillation (AF) is a common arrhythmia requiring rhythm control, but current medications have limited efficacy and significant side effects. This review explores potential drug targets and new methodologies, such as gene therapy and stem cell technologies, in the development of more effective treatments for AF. Recent advances in understanding the underlying mechanisms of AF are leading to a shift towards developing therapeutic agents targeting these mechanisms, with promising results in novel treatment approaches.
EXPERT OPINION ON DRUG DISCOVERY
(2021)
Article
Infectious Diseases
Anda Viksna, Darja Sadovska, Iveta Berge, Ineta Bogdanova, Annija Vaivode, Lauma Freimane, Inga Norvaisa, Iveta Ozere, Renate Ranka
Summary: The study found that whole genome sequencing is a valuable tool for rapid genotypic drug susceptibility testing for various anti-TB drugs. However, there are discrepancies between genotypic and phenotypic test results for certain drugs, so a combination of modern, validated phenotypic testing methods is needed for clinical decision-making.
BMC INFECTIOUS DISEASES
(2023)
Article
Microbiology
Emilia Gomez-Molero, Iker De-la-Pinta, Jordan Fernandez-Pereira, Uwe Gross, Michael Weig, Guillermo Quindos, Piet W. J. de Groot, Oliver Bader
Summary: Candida parapsilosis is a common cause of fungal bloodstream infections, especially in critically ill neonates or immunocompromised patients. Biofilm formation increases the risk of infection and complicates treatment, making it an important clinical parameter for guiding therapeutic choices.
Article
Microbiology
Lindsay B. Tulloch, Sandra Carvalho, Marta Lima, Richard J. Wall, Michele Tinti, Erika G. Pinto, Lorna MacLean, Susan Wyllie
Summary: A scalable resistance library screen (RES-Seq) has been developed to identify and prioritize anti-leishmanial compounds with novel mechanisms of actions. By screening against a panel of resistant cell lines, cross-resistance and shared mechanisms of action can be determined. Introducing DNA barcodes and using Illumina sequencing enables tracking of growth kinetics and relative fitness of multiple cell lines under compound selection.
Article
Chemistry, Medicinal
Lu Lu, Linda Akerbladh, Shabbir Ahmad, Vivek Konda, Sha Cao, Anthony Vocat, Louis Maes, Stewart T. Cole, Diarmaid Hughes, Mats Larhed, Peter Brandt, Anders Karlen, Sherry L. Mowbray
Summary: In this study, a series of novel quinolinyl pyrimidines were synthesized and evaluated for their antimicrobial activity. The compounds showed good inhibition against Gram-negative pathogens, but had limited activity against protozoan parasites.
ACS INFECTIOUS DISEASES
(2022)
Article
Chemistry, Medicinal
Cai Lin, Denise da Gama Jaen Batista, Ana Lia Mazzeti, Roberson Donola Girao, Gabriel Melo de Oliveira, Izet Karalic, Fabian Hulpia, Maria de Nazare C. Soeiro, Louis Maes, Guy Caljon, Serge Van Calenbergh
Summary: Chagas disease and leishmaniasis are poverty-related neglected tropical diseases that require safer and more effective drugs. This study explored purine nucleoside analogues as chemotherapeutic agents against Trypanosoma cruzi and Leishmania infections. The methyl analogue showed the best activity against both parasites and high selectivity against host cells. Oral administration reduced parasitemia levels and increased animal survival rates in a mouse model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Chris Van Ginneken, Miriam Ayuso, Lieselotte Van Bockstal, Steven Van Cruchten
Summary: Intrauterine growth restriction (IUGR) is commonly observed in pig production, resulting in differences in organ growth. Insufficient uteroplacental nutrient transfer is the main cause of IUGR. Supplementing arginine and glutamine in the sow's diet improves placenta growth and reduces IUGR incidence. IUGR piglets have higher mortality rates and morbidity. Surveillance during farrowing and individual nutrient supplementation can reduce mortality rates. However, long-term consequences of IUGR, including persistent structural deficits in organs, cannot be reversed.
MOLECULAR REPRODUCTION AND DEVELOPMENT
(2023)
Article
Infectious Diseases
Sarah Hendrickx, Guy Caljon
Summary: This study investigates the impact of host blood composition on Leishmania parasite transmission and sand fly survival. The results show that the levels of blood glucose inversely correlate with parasite burden, and appropriate levels of glucose can increase parasite load and the appearance of metacyclics. Additionally, higher levels of carbohydrates and insulin/IGF-1 favor sand fly survival.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Parasitology
Yang Zheng, Joachim Mueller, Stefan Kunz, Marco Siderius, Louis Maes, Guy Caljon, Norbert Mueller, Andrew Hemphill, Geert Jan Sterk, Rob Leurs
Summary: By combining structural elements of phosphodiesterase inhibitors with a nitroimidazole scaffold, the study aimed to improve antiparasitic efficacy by generating nitrosative stress.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2022)
Article
Chemistry, Medicinal
Cai Lin, Izet Karalic, An Matheeussen, Pim-Bart Feijens, Fabian Hulpia, Louis Maes, Guy Caljon, Serge Van Calenbergh
Summary: Leishmaniasis is a disease that causes high mortality and morbidity in tropical and subtropical regions of Africa, Asia, the Americas, and southern Europe. Limited resources are allocated for antileishmanial drug discovery. A study found that by interfering with the purine salvage pathway, a purine analogue can selectively hinder the growth and survival of the Leishmania parasite.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Parasitology
Dorien Mabille, Kayhan Ilbeigi, Sarah Hendrickx, Marzuq A. Ungogo, Fabian Hulpia, Cai Lin, Louis Maes, Harry P. de Koning, Serge Van Calenbergh, Guy Caljon
Summary: Animal trypanosomiasis is a parasitic disease with significant socio-economic impact. This study evaluated the potential use of antitrypanosomal nucleosides as a treatment for animal trypanosomiasis and identified promising compounds with excellent in vitro activity. Compound 7 and compound 8 exhibited broad spectrum anti-animal trypanosomiasis activity in mouse models, but with varying efficacy.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2022)
Article
Biology
Laura Dirkx, Sarah Hendrickx, Margot Merlot, Dimitri Bulte, Marick Starick, Jessy Elst, Andre Bafica, Didier G. Ebo, Louis Maes, Johan Van Weyenbergh, Guy Caljon
Summary: Long-term hematopoietic stem cells may serve as protective niches for the Leishmania parasite, leading to treatment failure in cases of visceral leishmaniasis. This study identified long-term hematopoietic stem cells as a niche with high parasite burdens in the bone marrow, which are more tolerant to antileishmanial drugs and contribute to relapse. A unique transcriptional signature in these cells was identified, showing overlap with human VL and HIV co-infected blood transcriptomes.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sarah Hendrickx, Dimitri Bulte, Dorien Mabille, Roxanne Mols, Mathieu Claes, Kayhan Ilbeigi, Rokaya Ahmad, Laura Dirkx, Sara Van Acker, Guy Caljon
Summary: The application of in vivo bioluminescent imaging in infectious disease research has significantly increased in recent years. This study compared the efficacy of two modified bioluminescent substrates, CycLuc1 and AkaLumine-HCl, with that of D-luciferin in vitro and in vivo, and found that CycLuc1 is an excellent alternative to D-luciferin, requiring lower doses for in vivo bioluminescent imaging in rodent models of leishmaniasis and African trypanosomiasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Dorien Mabille, Laura Dirkx, Sofie Thys, Marjorie Vermeersch, Daniel Montenye, Matthias Govaerts, Sarah Hendrickx, Peter Takac, Johan Van Weyenbergh, Isabel Pintelon, Peter Delputte, Louis Maes, David Perez-Morga, Jean-Pierre Timmermans, Guy Caljon
Summary: Trypanosoma brucei, the parasite responsible for sleeping sickness, rapidly and permanently colonizes the lungs and affects the immune response, potentially making individuals more susceptible to opportunistic infections.
NATURE COMMUNICATIONS
(2022)
Article
Nanoscience & Nanotechnology
Alexandru-Milentie Hada, Nina Burduja, Marco Abbate, Claudio Stagno, Guy Caljon, Louis Maes, Nicola Micale, Massimiliano Cordaro, Angela Scala, Antonino Mazzaglia, Anna Pipemo
Summary: Advanced nanoscale antimicrobials, combining noble metal nanoparticles with conventional antimicrobial drugs, are considered as the next generation of antimicrobial agents. The demand for rapid, eco-friendly, and relatively inexpensive synthetic approaches for nontoxic metallic nanostructures with unique physicochemical properties is increasing. A straightforward synthetic strategy using polymeric beta-cyclodextrin as the reducing and stabilizing agent has been proposed to produce monodispersed and stable gold-based nanoparticles, either as monometallic structures or core-shell bimetallic architectures with an external silver layer. In this article, the preparation of a supramolecular assembly between these nanoparticles and pentamidine, an antileishmanial drug with a wide range of therapeutic properties, is described. The physicochemical characterization of the supramolecular assembly was investigated by complementary spectroscopic techniques, and the role of PolyCD in the reduction/stabilization of metal nanoparticles was investigated for the first time by NMR spectroscopy.
BEILSTEIN JOURNAL OF NANOTECHNOLOGY
(2022)
Article
Agriculture, Dairy & Animal Science
Kevin Van Tichelen, Sara Prims, Miriam Ayuso, Lieselotte Van Bockstal, Celine Van Kerschaver, Mario Vandaele, Jeroen Degroote, Steven Van Cruchten, Joris Michiels, Chris Van Ginneken
Summary: The increase in litter sizes of sows over the past three decades has resulted in higher proportions of low birth weight piglets and increased pre-weaning mortality. This study investigated the use of a dense milk replacer to improve the performance of low birth weight piglets. The results showed no significant effect of the milk replacer on the survival or performance of the piglets, suggesting that perinatal management is more important for their survival than supplementation.
Article
Biochemistry & Molecular Biology
Yang Zheng, Susanne Schroeder, Georgi K. Kanev, Sanaa S. Botros, Samia William, Abdel-Nasser A. Sabra, Louis Maes, Guy Caljon, Carmen Gil, Ana Martinez, Irene G. Salado, Koen Augustyns, Ewald Edink, Maarten Sijm, Erik de Heuvel, Iwan J. P. de Esch, Tiffany van der Meer, Marco Siderius, Geert Jan Sterk, David Brown, Rob Leurs
Summary: This study investigated the potential of Schistosoma mansoni phosphodiesterase SmPDE4A as a new drug target for schistosomiasis. The researchers cloned, isolated, and characterized the full-length and catalytic domains of SmPDE4A. They found that SmPDE4A resembles human PDE4 more than parasite PDEs. Screening of PDE inhibitors identified tetrahydrophthalazinones and benzamides as potential hits, but further evaluation showed that the inhibitors were not effective against S. mansoni, suggesting that SmPDE4A is not a suitable target for anti-schistosomiasis therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pediatrics
Marina-Stefania Stroe, Lieselotte Van Bockstal, Allan Valenzuela, Miriam Ayuso, Karen Leys, Pieter Annaert, Sebastien Carpentier, Anne Smits, Karel Allegaert, Adrian Zeltner, Antonius Mulder, Chris Van Ginneken, Steven Van Cruchten
Summary: Animal models provide valuable information on human disease mechanisms and (patho)physiological factors affecting drug development. Nonclinical data is critical for understanding pediatric disease conditions and developing new drug therapies. This study aimed to develop a neonatal Gottingen Minipig model for investigating the impact of systemic hypoxia and therapeutic hypothermia on drug disposition in perinatal asphyxia.
FRONTIERS IN PEDIATRICS
(2023)
Article
Biochemistry & Molecular Biology
Yang Zheng, An Matheeussen, Louis Maes, Guy Caljon, Geert Jan Sterk, Rob Leurs
Summary: Malaria remains a significant health threat, causing thousands of deaths each year. This study aimed to enhance the antimalarial potency of a hit compound and discovered a promising analog with higher potency against Plasmodium falciparum. Several other analogs with potent antimalarial activity were also identified, which can be further optimized for potential antimalarial drug development.