Article
Chemistry, Medicinal
Prisca Lagardere, Romain Mustiere, Nadia Amanzougaghene, Sebastien Hutter, Marion Casanova, Jean-Francois Franetich, Shahin Tajeri, Aurelie Malzert-Freon, Sophie Corvaisier, Marc Since, Nadine Azas, Patrice Vanelle, Pierre Verhaeghe, Nicolas Primas, Dominique Mazier, Nicolas Masurier, Vincent Lisowski
Summary: In this study, several strategies were explored to improve the metabolic stability of a previously identified compound with promising antiplasmodial activity. Among the new compounds, the 2-aminocyclobutyl derivative 5g exhibited enhanced microsomal stability and maintained antiplasmodial activity against erythrocytic and hepatic stages of Plasmodium, without significant cytotoxicity against primary hepatocytes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Katja Mueller, Matthew P. Gibbins, Mark Roberts, Arturo Reyes-Sandoval, Adrian V. S. Hill, Simon J. Draper, Kai Matuschewski, Olivier Silvie, Julius Clemence R. Hafalla
Summary: Antigens from different origins, either from sporozoites or exo-erythrocytic forms, exhibit significant differences in immunogenicity. However, both types of antigens can be effectively targeted and recognized by vaccine-induced effector CD8(+) T cells, leading to high levels of protection. This finding has important implications for antigen prioritization in next-generation pre-erythrocytic malaria vaccines.
EMBO MOLECULAR MEDICINE
(2021)
Article
Agriculture, Dairy & Animal Science
Mikas Ilgunas, Tanja Himmel, Josef Harl, Mindaugas Dagys, Gediminas Valkiunas, Herbert Weissenboeck
Summary: This study aimed to investigate avian haemosporidian parasites infecting owls in Europe and study their tissue stages. The study discovered seven new genetic variants of the parasites and identified the tissue development stages in the brains, heart muscles, and kidneys of infected birds.
Article
Immunology
Nan Jiun Yap, Hanisah Hossain, Thamayanthi Nada-Raja, Romano Ngui, Azdayanti Muslim, Boon-Peng Hoh, Loke Tim Khaw, Khamisah Abdul Kadir, Paul Cliff Simon Divis, Indra Vythilingam, Balbir Singh, Yvonne Ai-Lian Lim
Summary: The study identified various simian malaria parasites in indigenous communities living on the forest fringes in Malaysia, highlighting the importance of using molecular tools to detect newly emerging malaria parasites in humans.
EMERGING INFECTIOUS DISEASES
(2021)
Article
Chemistry, Medicinal
William Nguyen, Madeline G. Dans, Anna Ngo, Maria R. Gancheva, Ornella Romeo, Sandra Duffy, Tania F. de Koning-Ward, Kym N. Lowes, Helene Jousset Sabroux, Vicky M. Avery, Danny W. Wilson, Paul R. Gilson, Brad E. Sleebs
Summary: The phenylsulfonyl piperazine class has been identified as a specific inhibitor of erythrocyte invasion by P. falciparum parasites, showing antimalarial activity and potency against multidrug resistant strains. The optimized compounds also exhibit weak activity against sexual stage gametocytes, making them potentially useful tools for studying Plasmodium erythrocyte invasion.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Immunology
Kelvin Mokaya Abuga, William Jones-Warner, Julius Clemence R. Hafalla
Summary: Despite challenges, radiation-attenuated sporozoites as the 'gold standard' for malaria vaccine development provide a crucial platform for understanding the host-parasite immunological crosstalk in the tissue environments of the skin and the liver.
PARASITE IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Brodie L. Bailey, William Nguyen, Anna Ngo, Christopher D. Goodman, Maria R. Gancheva, Paola Favuzza, Laura M. Sanz, Francisco-Javier Gamo, Kym N. Lowes, Geoffrey I. McFadden, Danny W. Wilson, Benoit Laleu, Stephen Brand, Paul F. Jackson, Alan F. Cowman, Brad E. Sleebs
Summary: The study identified a triazolopyrimidine compound with good activity against Plasmodium falciparum and high selectivity against human cells, but faced challenges such as slow onset of action and low aqueous solubility. Further optimization is needed for its development as a potential partner in anti-malarial treatment.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Lenna Rosanie Cordero Mallaupoma, Barbara Karina de Menezes Dias, Maneesh Kumar Singh, Rute Isabel Honorio, Myna Nakabashi, Camila de Menezes Kisukuri, Marcio Weber Paixao, Celia R. S. Garcia
Summary: Melatonin can synchronize the intraerythrocytic cycle of the parasite by triggering a specific signaling cascade. Compounds with certain chemical structures have inhibitory effects on the proliferation of malaria parasites, indicating their potential as new antimalarial drugs. The study found that certain synthetic compounds can inhibit different chloroquine-resistant strains of the parasite. In addition, melatonin affects the parasite load and modulates the expression of signaling components, providing a focus for further research.
Article
Immunology
Andrea A. Berry, Joshua M. Obiero, Mark A. Travassos, Amed Ouattara, Drissa Coulibaly, Matthew Adams, Rafael Ramiro de Assis, Aarti Jain, Omid Taghavian, Andrew Sy, Rie Nakajima, Algis Jasinskas, Matthew B. Laurens, Shannon Takala-Harrison, Bourema Kouriba, Abdoulaye K. Kone, Ogobara K. Doumbo, B. Kim Lee Sim, Stephen L. Hoffman, Christopher V. Plowe, Mahamadou A. Thera, Philip L. Felgner, Kirsten E. Lyke
Summary: This study assessed IgG and IgA antibody responses in adult sera collected during CHMI studies and in Malian children, and identified differences in the immunoproteome among naive individuals and exposed individuals. It also expanded the list of pre-erythrocytic antigens recognized by the immune system and highlighted the potential of IgA responses as vaccine candidates.
Review
Immunology
Vitomir Djokic, Sandra C. Rocha, Nikhat Parveen
Summary: Malaria is transmitted by Anopheles mosquitoes, while babesiosis is caused by ticks. Both diseases have similarities and differences, with inflammatory immune responses playing a role in disease severity.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Wai Kwan Tang, Camila H. Coelho, Kazutoyo Miura, Bergeline C. Nguemwo Tentokam, Nichole D. Salinas, David L. Narum, Sara A. Healy, Issaka Sagara, Carole A. Long, Patrick E. Duffy, Niraj H. Tolia
Summary: Pfs230D1 is a highly functional vaccine antigen for malaria transmission-blocking, and this study characterized a panel of human monoclonal antibodies (hmAbs) elicited in vaccinees immunized with Pfs230D1. The results showed diverse transmission-reducing activity of these hmAbs, but all bound to Pfs230D1 with nanomolar affinity. By constructing a high-resolution epitope map, the researchers identified that potent transmission-reducing hmAbs bound to one side of Pfs230D1, while non-potent hmAbs bound to the other side, and the second domain of Pfs230D1 occluded the epitopes for non-potent hmAbs. This study provides valuable insights for the structure-based design of enhanced immunogens and the development of diagnostic assays for measuring the transmission-reducing response.
Article
Multidisciplinary Sciences
Seong-Kyun Lee, Leanne M. Low, John F. Andersen, Lee M. Yeoh, Paola Carolina Valenzuela Leon, Damien R. Drew, Johannes S. P. Doehl, Eric Calvo, Louis H. Miller, James G. Beeson, Karthigayan Gunalan
Summary: This study used a transgenic parasite to investigate the invasion process mediated by PvAMA1. The findings showed that PfRON2 had no effect on the invasion of transgenic parasites expressing PvAMA1, while PvRON2p blocked the invasion of PvAMA1 transgenic parasites. Additionally, the study revealed that PvAMA1 directly interacts with erythrocytes during invasion, and the invasion blocking by PvRON2p may be due to its interference with PvAMA1 binding to erythrocytes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Yuxiang Dong, Yogesh Sonawane, Steven P. Maher, Anne-Marie Zeeman, Victor Chaumeau, Amelie Vantaux, Caitlin A. Cooper, Francis C. K. Chiu, Eileen Ryan, Jenna McLaren, Gong Chen, Sergio Wittlin, Benoit Witkowski, Francois Nosten, Kamaraj Sriraghavan, Dennis E. Kyle, Clemens H. M. Kocken, Susan A. Charman, Jonathan L. Vennerstrom
Summary: This study investigates the metabolism and activity of the catechol derivative RC-12 (WR 27653). The results suggest that the metabolites of RC-12 may contribute to its superior efficacy against liver-stage malaria parasites in rhesus monkeys compared to humans. However, none of the identified metabolites showed activity against Plasmodium vivax or Plasmodium cynomolgi liver-stage parasites.
Article
Agriculture, Dairy & Animal Science
Carolina Hernandez-Lara, Melanie Duc, Mikas Ilgunas, Gediminas Valkiunas
Summary: Haemoproteus parasites are widespread avian blood parasites belonging to the Haemoproteidae (Haemosporida). While blood stages of these pathogens have been relatively well studied, the exo-erythrocytic (tissue) stages remain unidentified for most species. Recent histopathological studies have shown that these parasites can significantly impact bird organs during tissue merogony. This study specifically investigated the exo-erythrocytic development of Haemoproteus attenuatus in flycatchers, providing new insights into the potential damage caused by these parasites in the lungs.
Article
Immunology
Yifan Wu, Shiguang Huang, Siyu Xiao, Jian He, Fangli Lu
Summary: Blocking galectin-receptor interactions affects liver immunopathology during Plasmodium berghei ANKA infection in mice, leading to decreased host survival rate, increased parasite burden, and exacerbated liver pathology.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemical Research Methods
Ana M. Untaroiu, Maureen A. Carey, Jennifer L. Guler, Jason A. Papin
BMC BIOINFORMATICS
(2019)
Article
Microbiology
Awtum M. Brashear, Adam C. Huckaby, Qi Fan, Luke J. Dillard, Yubing Hu, Yuling Li, Yan Zhao, Zenglei Wang, Yaming Cao, Jun Miao, Jennifer L. Guler, Liwang Cui
FRONTIERS IN MICROBIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Jennifer M. McDaniels, Adam C. Huckaby, Sabrina A. Carter, Sabrina Lingeman, Audrey Francis, Molly Congdon, Webster Santos, Pradipsinh K. Rathod, Jennifer L. Guler
Summary: Extrachromosomal DNA contributes to antimalarial resistance in Plasmodium falciparum, showing unique characteristics and potential molecular mechanisms, possibly maintained through shared features with the mitochondrial genome. Discovery of ecDNA in this organism has wide-reaching implications for developing new strategies to target resistance development.
MOLECULAR MICROBIOLOGY
(2021)
Article
Infectious Diseases
Kennedy Kassaza, Anna C. Long, Jennifer M. McDaniels, Mharlove Andre, Wasswa Fredrickson, Dan Nyehangane, Patrick Orikiriza, Darwin J. Operario, Joel Bazira, Juliet A. Mwanga-Amumpaire, Christopher C. Moore, Jennifer L. Guler, Yap Boum
Summary: Quantitative PCR followed by High-Resolution Melt (HRM) analysis was used to assess pfcrt mutations in clinical samples from Southwestern Uganda. The study showed that the method was flexible and successful in detecting resistance alleles in different types of clinical samples. The predominant haplotype was CVIET in the clinical samples, but there were significant regional variations.
Article
Infectious Diseases
Mukhethwa Munzhedzi, Elizabeth T. Rogawski McQuade, Jennifer L. Guler, Piper E. Shifflett, Sara Krivacsy, Rebecca Dillingham, Pascal O. Bessong
Summary: The study demonstrates that participants have appropriate knowledge about malaria transmission and a positive treatment-seeking behavior. However, economic barriers are responsible for the inadequate use of bed nets. Therefore, distribution of bed nets to the community should be considered to improve practice of malaria prevention measures. Furthermore, knowledge of signs and symptoms and appropriate malaria treatment was limited, and initiatives to improve awareness on these topics should be continued.
Article
Genetics & Heredity
Shiwei Liu, Adam C. Huckaby, Audrey C. Brown, Christopher C. Moore, Ian Burbulis, Michael J. McConnell, Jennifer L. Guler
Summary: This study presents a single-cell sequencing pipeline for the intracellular parasite Plasmodium falciparum and provides a framework for optimizing single-cell amplification and variant analysis in challenging genomes. The work enables detection of parasite heterogeneity contributing to P. falciparum adaptation.
Article
Biochemical Research Methods
Maureen Carey, Gregory Medlock, Michal Stolarczyk, William Petri Jr, Jennifer Guler, Jason Papin
Summary: Protozoan parasites cause diverse diseases with global impacts. Research on these parasites is limited by economic and experimental constraints. To overcome this challenge, the authors conducted a functional comparative analysis of 192 protozoan parasite genomes and constructed metabolic network models. This resource can help predict species-specific functions, contextualize experimental results, and optimize selection of experimental systems for fastidious species.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Microbiology
Audrey C. Brown, Michelle D. Warthan, Anush Aryal, Shiwei Liu, Jennifer L. Guler
Summary: There is a dire need for effective treatments against microbial pathogens. Yet, the continuing emergence of drug resistance necessitates a deeper knowledge of how pathogens respond to treatments. We assessed the effect of nutrient limitation on the protozoan parasite that causes malaria and demonstrated that short-term growth under physiologically relevant mild nutrient stress triggers increased tolerance of a potent antimalarial drug. This finding highlights the important connections among nutrient levels, protective cellular pathways, and resistance evolution.
Article
Biochemical Research Methods
XuHai Huang, Karina Torres-Castro, Walter Varhue, Armita Salahi, Ahmed Rasin, Carlos Honrado, Audrey Brown, Jennifer Guler, Nathan S. Swami
Summary: This study introduces a novel method for cell separation using dielectrophoresis, which achieves efficient and precise separation by designing specific device geometries. Experimental validation on healthy and fixed red blood cells demonstrates the effectiveness of this method, highlighting its potential for further applications.
Review
Parasitology
Audrey C. Brown, Jennifer L. Guler
TRENDS IN PARASITOLOGY
(2020)