Article
Microbiology
Bart Cuypers, Pieter Meysman, Ionas Erb, Wout Bittremieux, Dirk Valkenborg, Geert Baggerman, Inge Mertens, Shyam Sundar, Basudha Khanal, Cedric Notredame, Jean-Claude Dujardin, Malgorzata A. Domagalska, Kris Laukens
Summary: Aneuploidy has a significant impact on the transcriptome, proteome, and metabolome of Leishmania donovani, leading to disruptions in stochiometric balances and metabolic differences between aneuploid strains. However, protein complex subunits and non-cytoplasmic proteins show attenuations in dosage effects. The differentially expressed proteins are enriched for those involved in protein metabolism. These findings suggest that aneuploidy in Leishmania can be adaptive and make it an attractive model for studying protein homeostasis in the context of aneuploidy.
Article
Microbiology
Marlene Jara, Michael Barrett, Ilse Maes, Clement Regnault, Hideo Imamura, Malgorzata Anna Domagalska, Jean-Claude Dujardin
Summary: Microorganisms have the ability to enter a quiescent state as a survival strategy under unfavorable conditions. This study investigated the molecular and metabolic features of quiescent Leishmania parasites using transcriptomic and metabolomic analyses.
Article
Multidisciplinary Sciences
Aretha Chan, Jose-Mauricio Ayala, Fernando Alvarez, Ciriaco Piccirillo, George Dong, David Langlais, Martin Olivier
Summary: This study analyzed the early innate inflammatory events during L. major infection, confirming the significant role of the virulence factor GP63 in providing favorable conditions for host cell infection. The data suggest that GP63 does not greatly influence pathogen-induced inflammatory cell recruitment, but rather affects their activation status and effector function, as well as potentially influencing the internalization of promastigotes during early infection.
Article
Infectious Diseases
Nagendra N. Mishra, Rodrigo de Paula Baptista, Truc T. Tran, Christian K. Lapitan, Cristina Garcia-de-la-Maria, Jose M. Miro, Richard A. Proctor, Arnold S. Bayer
Summary: This study reveals that Streptococcus mitis-oralis subgroup is an important human pathogen. More than 25% of S. mitis-oralis strains develop rapid and high-level resistance to daptomycin when exposed to the drug in vitro. This resistance is often associated with changes in membrane phenotypes and metabolic pathways.
Article
Microbiology
Aya Hefnawy, Gabriel Negreira, Marlene Jara, James A. Cotton, Ilse Maes, Erika D'Haenens, Hideo Imamura, Bart Cuypers, Pieter Monsieurs, Christina Mouchtoglou, Hans De Winter, Isabel Pintelon, Jean-Pierre Timmermans, Matt Berriman, Mandy Sanders, Julio Martin, Geraldine de Muylder, Jean-Claude Dujardin, Yann G. -J. Sterckx, Malgorzata Anna Domagalska
Summary: Through prospective drug resistance (DR) studies, a new DR mechanism involving the dynamin protein LdoDLP1 was discovered in Leishmania donovani, shedding light on the practical relevance of such studies.
Article
Microbiology
Aya Hefnawy, Gabriel Negreira, Marlene Jara, James A. Cotton, Ilse Maes, Erika D'Haenens, Hideo Imamura, Bart Cuypers, Pieter Monsieurs, Christina Mouchtoglou, Hans De Winter, Isabel Pintelon, Jean-Pierre Timmermans, Matt Berriman, Mandy Sanders, Julio Martin, Geraldine de Muylder, Jean-Claude Dujardin, Yann G-J Sterckx, Malgorzata Anna Domagalska
Summary: The study demonstrates the importance of prospective drug resistance (DR) studies for neglected tropical diseases (NTDs) using Leishmania donovani as a paradigm. By experimentally selecting resistance to a promising compound for visceral leishmaniasis and characterizing resistant parasites, a new DR mechanism involving LdoDLP1 was discovered. This highlights the practical relevance of prospective DR studies.
Article
Sport Sciences
Heath M. Burton, Anthony S. Wolfe, Emre Vardarli, Remzi Satiroglu, Edward F. Coyle
Summary: The study found that reducing daily steps can affect acute and short-term adaptations to intense aerobic training, especially showing more pronounced effects on metabolic responses and stress reactions.
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
(2021)
Review
Biochemistry & Molecular Biology
Koushik Das, Tomoyoshi Nozaki
Summary: Eukaryotic cells have membrane-enclosed organelles that have distinct functions and characteristics. The distribution and movement of lipids and proteins play a crucial role in determining the identity of each organelle. Studying lipid transport mechanisms in protists, such as Leishmania donovani, can contribute to our understanding of parasitism and eukaryotic evolution. Through bioinformatics analysis, we identified potential lipid transfer proteins in L. donovani and discussed their implications in parasite biology and potential therapeutic targets against visceral leishmaniasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Fernanda V. Cabral, Michela Cerone, Saydulla Persheyev, Cheng Lian, Ifor D. W. Samuel, Martha S. Ribeiro, Terry K. Smith
Summary: The emergence of drug resistance in cutaneous leishmaniasis has become a major problem. Photodynamic therapy has shown effectiveness against drug-resistant strains and may be an attractive strategy for treatment.
Article
Immunology
Keerti, Narendra Kumar Yadav, Sumit Joshi, Sneha Ratnapriya, Amogh Anant Sahasrabuddhe, Anuradha Dube
Summary: This study demonstrates the effectiveness of a chemo-immunotherapeutic strategy in improving immune response and reducing parasitic load in visceral leishmaniasis. The combination of recombinant proteins and a low dose of antileishmanial drug shows promise for controlling the infection with minimal side effects and drug resistance emergence.
JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION
(2023)
Article
Agriculture, Dairy & Animal Science
L. Cattaneo, F. Piccioli-Cappelli, A. Minuti, E. Trevisi
Summary: There are significant differences in cow yields and body sizes between their first and second lactations. The transition period, which is the most critical phase of the lactation cycle, was compared between cows at different parities. The study examined metabolic and endocrine responses and found that cows during their second lactation had higher dry matter intake and body weight, as well as greater milk yield but reduced persistency compared to their first lactation. Additionally, differences in milk composition and markers of metabolism, inflammation, and liver function were observed between the two lactations.
JOURNAL OF DAIRY SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Andreina Henriquez-Figuereo, Esther Moreno, Carmen Sanmartin, Daniel Plano
Summary: This work focuses on the design, synthesis, and biological activities of new selenoester derivatives and thioester homologs with potential as therapeutic candidates for leishmaniasis. These compounds showed structural similarities to antileishmanial drugs and exhibited high sensitivity against Leishmania infantum, the causative agent of visceral leishmaniasis. Four selanylacetic acid derivatives demonstrated significant leishmanicidal characteristics and pharmacological synergism with the oral drug miltefosine.
Article
Chemistry, Medicinal
Narender Goel, Vivek Kumar Gupta, Aakriti Garg, Arpita Bhoumik, Raju Biswas, Ramalingam Natarajan, Hemanta K. Majumder, Parasuraman Jaisankar
Summary: Holanamine isolated from Holarrhena pubescens showed significant antileishmanial activity against Leishmania donovani, better than the standard drug miltefosine. It inhibited LdToP1B enzyme without affecting human topoisomerase, and its antileishmanial activity is attributed to hydrogen bonding and hydrophobic interactions with the enzyme. Holanamine induced apoptotic-like cell death in Leishmania by generating reactive oxygen species and disrupting mitochondrial membrane potential.
ACS INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Hermali Silva, Achala Liyanage, Theja Deerasinghe, Vasana Chandrasekara, Kalaivani Chellappan, Nadira D. Karunaweera
Summary: This study is the first detailed investigation of treatment failures in CL in Sri Lanka, revealing a relatively high rate of treatment failure especially in patients over 20 years old. It underscores the importance of further research into the pathogenesis of treatment failures and the need to review existing treatment protocols to introduce more effective strategies.
Article
Chemistry, Medicinal
Jared T. Hammill, Vitaliy M. Sviripa, Liliia M. Kril, Diana Ortiz, Corinne M. Fargo, Ho Shin Kim, Yizhe Chen, Jonah Rector, Amy L. Rice, Malgorzata A. Domagalska, Kristin L. Begley, Chunming Liu, Vivek M. Rangnekar, Jean-Claude Dujardin, David S. Watt, Scott M. Landfear, R. Kiplin Guy
Summary: Leishmaniasis, a disease affecting roughly 12 million individuals globally, is caused by protozoa of the Leishmania species. Most existing drugs for leishmaniasis are toxic, expensive, difficult to administer, and prone to drug resistance. The new class of antileishmanial leads, 3-arylquinolines, show promise in blocking parasite proliferation with good selectivity relative to host cells. Early leads like 34 and 27 demonstrate potent activity against different Leishmania species and potential for drug development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Immunology
James Peng, Jamin Liu, Sabrina A. Mann, Anthea M. Mitchell, Matthew T. Laurie, Sara Sunshine, Genay Pilarowski, Patrick Ayscue, Amy Kistler, Manu Vanaerschot, Lucy M. Li, Aaron McGeever, Eric D. Chow, Carina Marquez, Robert Nakamura, Luis Rubio, Gabriel Chamie, Diane Jones, Jon Jacobo, Susana Rojas, Susy Rojas, Valerie Tulier-Laiwa, Douglas Black, Jackie Martinez, Jamie Naso, Joshua Schwab, Maya Petersen, Diane Havlir, Joseph DeRisi
Summary: The prevalence of West Coast SARS-CoV-2 variants and their transmission rate showed a modest increase in a community testing setting in San Francisco during January 2021.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Immunology
Tara MacCannell, Joshua Batson, Brandon Bonin, K. C. Astha, Rebecca Quenelle, Betsy Strong, Wen Lin, Sarah L. Rudman, David Dynerman, Patrick Ayscue, George Han, Amy Kistler, Margarita Elsa Villarino
Summary: This study investigates the outbreaks of SARS-CoV-2 in long-term care facilities (LTCFs) in Santa Clara County, California. The findings reveal a pattern of rapid and sustained transmission after a single introduction of the virus, with staff playing a key role in transmission within and between facilities. Infection control, testing, and occupational policies are crucial in reducing exposure and transmission risk for staff and ensuring the safety of LTCF residents.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Biotechnology & Applied Microbiology
Abraham Lin, Joey De Backer, Delphine Quatannens, Bart Cuypers, Hanne Verswyvel, Edgar Cardenas de la Hoz, Bart Ribbens, Vasiliki Siozopoulou, Jonas van Audenaerde, Elly Marcq, Filip Lardon, Kris Laukens, Steve Vanlanduit, Evelien Smits, Annemie Bogaerts
Summary: Research shows that non-thermal plasma (NTP) treatment can reduce melanoma burden and prolong survival, while enhancing the cancer-immunity cycle. This finding helps develop new treatment options and guide rational combination strategies to address challenges in melanoma therapy.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2022)
Article
Microbiology
Emmanuel Riviere, Lennert Verboven, Anzaan Dippenaar, Sander Goossens, Elise De Vos, Elizabeth Streicher, Bart Cuypers, Kris Laukens, Fathia Ben-Rached, Timothy C. Rodwell, Arnab Pain, Robin M. Warren, Tim H. Heupink, Annelies Van Rie
Summary: Studies have shown that variants in bedaquiline-resistance genes can occur in isolates from bedaquiline-naive patients. The prevalence of these variants in such patients is high, but the number of isolates exhibiting phenotypic resistance is very low. There is an association between these variants and the lineage of Mycobacterium tuberculosis, leading to a lineage-dependent difference in bedaquiline phenotype. Future studies should investigate the impact of these variants on the acquisition of bedaquiline resistance and treatment outcomes.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Public, Environmental & Occupational Health
Celine Perier, Emmanuel Nasinghe, Isabelle Charles, Leoson Junior Ssetaba, Vida Ahyong, Derek Bangs, P. Robert Beatty, Nadine Czudnochowski, Amy Diallo, Eli Dugan, Jacqueline M. Fabius, Hildy Fong Baker, Jackson Gardner, Stephen Isaacs, Birungi Joanah, Katrina Kalantar, David Kateete, Matt Knight, Maria Krasilnikov, Nevan J. Krogan, Chaz Langelier, Eric Lee, Lucy M. Li, Daniel Licht, Katie Lien, Zilose Lyons, Gerald Mboowa, Ivan Mwebaza, Savannah Mwesigwa, Geraldine Nalwadda, Robert Nichols, Maria Elena Penaranda, Sarah Petnic, Maira Phelps, Stephen J. Popper, Michael Rape, Arthur Reingold, Richard Robbins, Oren S. Rosenberg, David F. Savage, Samuel Schildhauer, Matthew L. Settles, Ivan Sserwadda, Sarah Stanley, Cristina M. Tato, Alexandra Tsitsiklis, Erik Van Dis, Manu Vanaerschot, Joanna Vinden, Jeffery S. Cox, Moses L. Joloba, Julia Schaletzky
Summary: Science education and research are crucial for driving development in low- and middle-income countries. The Alliance's partnership program, the MU/UCB Biosciences Training Program, provides valuable research training opportunities for students at Makerere University, enhancing their research capacity and contributing to local economic development.
GLOBAL HEALTH ACTION
(2022)
Article
Microbiology
Bart Cuypers, Pieter Meysman, Ionas Erb, Wout Bittremieux, Dirk Valkenborg, Geert Baggerman, Inge Mertens, Shyam Sundar, Basudha Khanal, Cedric Notredame, Jean-Claude Dujardin, Malgorzata A. Domagalska, Kris Laukens
Summary: Aneuploidy has a significant impact on the transcriptome, proteome, and metabolome of Leishmania donovani, leading to disruptions in stochiometric balances and metabolic differences between aneuploid strains. However, protein complex subunits and non-cytoplasmic proteins show attenuations in dosage effects. The differentially expressed proteins are enriched for those involved in protein metabolism. These findings suggest that aneuploidy in Leishmania can be adaptive and make it an attractive model for studying protein homeostasis in the context of aneuploidy.
Article
Immunology
Katlijn De Meulenaere, Surendra Kumar Prajapati, Elizabeth Villasis, Bart Cuypers, Johanna Helena Kattenberg, Bernadine Kasian, Moses Laman, Leanne J. Robinson, Dionicia Gamboa, Kris Laukens, Anna Rosanas-Urgell
Summary: This study uncovered a band 3-mediated invasion pathway in P. vivax and identified band 3 as a receptor for P. vivax invasion. The study also identified potential band 3 ligands and highlighted the PvTRAg genes as promising candidates for further research.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Samuel Munalula Munjita, Given Moonga, Andrew Nalishuwa Mukubesa, Joseph Ndebe, Benjamin Mubemba, Manu Vanaerschot, Cristina Tato, John Tembo, Nathan Kapata, Simbarashe Chitanga, Katendi Changula, Mashiro Kajihara, Walter Muleya, Ayato Takada, Elisabeth Fichet-Calvet, Alimuddin Zumla, Hirofumi Sawa, Matthew Bates, Sody Munsaka, Edgar Simulundu
Summary: This study investigated the presence of mammarenaviruses and co-infecting helminths in rodents and small mammals in Zambia. The Luna virus (LUAV) genome was detected in a small percentage of rodents, with higher levels found in semen. Co-infections between LUAV and helminths were observed. Age, nematode and cestode infections, and being male were associated with increased odds of LUAV detection.
Review
Pharmacology & Pharmacy
Abraham Lin, Maxime Sahun, Eline Biscop, Hanne Verswyvel, Jorrit De Waele, Joey De Backer, Claudia Theys, Bart Cuypers, Kris Laukens, Wim Vanden Berghe, Evelien Smits, Annemie Bogaerts
Summary: This study aimed to investigate the mechanisms of NTP therapy sensitivity and resistance by using the first-ever NTP-resistant cell line derived from sensitive melanoma cells. The cells were exposed to NTP for 12 weeks and evaluated against the parental control cells. Transcriptome sequencing and metabolic analysis revealed a preference towards aerobic glycolysis and increased vulnerability to lipid peroxidation and ferroptosis in NTP-resistant cells.
DRUG RESISTANCE UPDATES
(2023)
Article
Chemistry, Medicinal
Lorenzo Tagliazucchi, Ana Perea-Martinez, Greta Fiorini, Jose Ignacio Manzano, Filippo Genovese, Raquel Garcia-Hernandez, Diego Pinetti, Francisco Gamarro, Maria Paola Costi
Summary: As leishmaniasis becomes increasingly difficult to treat with current therapies, understanding the molecular mechanisms of drug resistance and treatment failure is crucial for drug discovery and development. This study investigates the biochemical pathways of THP-1 human monocytes infected with different Leishmania infantum clinical isolates, and identifies overexpressed proteins associated with drug resistance. The findings provide insights into new targets for combating drug resistance and treatment failure, and highlight the importance of a dual host-guest pharmacological approach.
ACS INFECTIOUS DISEASES
(2023)
Article
Cell Biology
Tom Breugelmans, Wout Arras, Baptiste Oosterlinck, Aranzazu Jauregui-Amezaga, Michael Somers, Bart Cuypers, Kris Laukens, Joris G. De Man, Heiko U. De Schepper, Benedicte Y. De Winter, Annemieke Smet
Summary: This study investigates the role of MUC13 in disrupting epithelial barrier integrity and the involvement of MUC1 in inflammatory bowel diseases (IBD). The results demonstrate that MUC13 overexpression affects the expression of junctional proteins and barrier mediators, leading to intestinal barrier dysfunction. Furthermore, MUC13 modulates several signaling pathways, including JAK1/STAT3, SNAI1/ZEB1, and ROCK2/MAPK, in cooperation with MUC1. The findings suggest that aberrant MUC13 signaling plays an active role in inducing intestinal barrier dysfunction during inflammation.
Article
Chemistry, Medicinal
J. Jonathan Nue-Martinez, David Cisneros, Maria del Valle Moreno-Blazquez, Cristina Fonseca-Berzal, Jose Ignacio Manzano, Damien Kraeutler, Marzuq A. Ungogo, Maha A. Aloraini, Hamza A. A. Elati, Alexandra Ibanez-Escribano, Laura Lagartera, Tomas Herraiz, Francisco Gamarro, Harry P. de Koning, Alicia Gomez-Barrio, Christophe Dardonville
Summary: In this study, we synthesized a series of analogues and conducted antiprotozoal screening and SAR studies of kDNA binders for trypanosomatid parasites. We found that compound 3a exhibited good activity and selectivity against all three parasites, making it a promising candidate for in vivo studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Katlijn De Meulenaere, Wim L. Cuypers, Julia M. Gauglitz, Pieter Guetens, Anna Rosanas-Urgell, Kris Laukens, Bart Cuypers
Summary: This study investigates the potential of nanopore adaptive sampling to enrich Plasmodium falciparum reads during sequencing, and the results show that adaptive sampling mode can significantly enrich the reads of P. falciparum. By sequencing patient blood samples, adaptive nanopore sequencing can efficiently enrich and sequence the genome of P. falciparum, simplifying the timeline from blood collection to parasite sequencing. This technology can be used for monitoring genetic markers or generating nearly complete genomes, and its mobility makes it easily applicable on-site in endemic areas.
Article
Biochemistry & Molecular Biology
James M. Murithi, Ioanna Deni, Charisse Flerida A. Pasaje, John Okombo, Jessica L. Bridgford, Nina F. Gnadig, Rachel L. Edwards, Tomas Yeo, Sachel Mok, Anna Y. Burkhard, Olivia Coburn-Flynn, Eva S. Istvan, Tomoyo Sakata-Kato, Maria G. Gomez-Lorenzo, Annie N. Cowell, Kathryn J. Wicht, Claire Le Manach, Gavreel F. Kalantarov, Sumanta Dey, Maelle Duffey, Benoit Laleu, Amanda K. Lukens, Sabine Ottilie, Manu Vanaerschot, Ilya N. Trakht, Francisco-Javier Gamo, Dyann F. Wirth, Daniel E. Goldberg, Audrey R. Odom John, Kelly Chibale, Elizabeth A. Winzeler, Jacquin C. Niles, David A. Fidock
Summary: This study identifies the transporter ABCI3 and the chloroquine resistance transporter PfCRT as key players in drug resistance in Plasmodium falciparum. The mode of action of the compound imidazopyridine is attributed to inhibition of heme detoxification.
CELL CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Robert L. Summers, Charisse Flerida A. Pasaje, Joao P. Pisco, Josefine Striepen, Madeline R. Luth, Krittikorn Kumpornsin, Emma F. Carpenter, Justin T. Munro, De Lin, Andrew Plater, Avinash S. Punekar, Andrew M. Shepherd, Sharon M. Shepherd, Manu Vanaerschot, James M. Murithi, Kelly Rubiano, Asli Akidi, Sabine Ottilie, Nimisha Mittal, A. Hazel Dilmore, Madalyn Won, Rebecca E. K. Mandt, Kerry McGowen, Edward Owen, Chris Walpole, Manuel Llinas, Marcus C. S. Lee, Elizabeth A. Winzeler, David A. Fidock, Ian H. Gilbert, Dyann F. Wirth, Jacquin C. Niles, Beatriz Baragana, Amanda K. Lukens
Summary: In this study, we identified and validated the Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS) as an important, druggable target. Genetic and chemical validation confirmed that mutations in PfAcAS confer resistance to two antiplasmodial compounds and that these compounds directly inhibit the enzyme. We also found that PfAcAS is essential for asexual growth and involved in the epigenetic regulation of gene expression.
CELL CHEMICAL BIOLOGY
(2022)