Article
Oncology
John R. Mackey, Justine Lai, Utkarsh Chauhan, Erwan Beauchamp, Wei-Feng Dong, Darryl Glubrecht, Yie-Wei Sim, Sunita Ghosh, Gilbert Bigras, Raymond Lai, Luc G. Berthiaume
Summary: The study demonstrates that NMT1 is quantifiable in normal and most transformed breast epithelial tissues and is associated with higher histologic grade, higher Ki67, and lower hormone receptor expression. On the other hand, NMT2 is detected in normal breast tissue but largely undetectable in breast cancer, and its presence correlates with poorer overall survival and worse biological features. Furthermore, treatment with NMT inhibitor PCLX-001 shows potential for inhibiting breast cancer cell viability in vitro and inhibiting tumor growth in vivo, indicating the need for further clinical trials.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Review
Medicine, General & Internal
Hong Wang, Xin Xu, Jiayi Wang, Yongxia Qiao
Summary: NMT1 is an essential enzyme that transfers myristoyl groups to proteins, and its elevated expression is associated with various types of tumors and poor survival in cancer patients. This review discusses the mechanisms by which NMT1 is involved in tumor development, including oncogene signaling, cellular metabolism, and endoplasmic reticulum stress. The review also introduces NMT inhibitors for cancer treatment, providing potential therapeutic avenues for targeting NMT1.
ANNALS OF MEDICINE
(2023)
Article
Biology
Florian Becker, Simon Fuchs, Lukas Refisch, Friedel Drepper, Wolfgang Bildl, Uwe Schulte, Shuo Liang, Jonas Immanuel Heinicke, Sierra C. Hansen, Clemens Kreutz, Bettina Warscheid, Bernd Fakler, Evgeny Mymrikov, Carola Hunte
Summary: This study reveals that calcium binding and myristoylation independently affect the conformation and functions of human CHP3. Calcium binding increases the flexibility and hydrophobicity of CHP3, indicating an open conformation. Myristoylation enhances the flexibility of CHP3 and decreases its affinity to NHE1 independently of the bound ion.
Review
Immunology
Bin Wang, Tong Dai, Wenhuan Sun, Yujun Wei, Jiang Ren, Long Zhang, Mengdi Zhang, Fangfang Zhou
Summary: Protein N-myristoylation is a critical fatty acylation process catalyzed by N-myristoyltransferases in eukaryotes, playing key roles in signal transduction, cellular localization, and immune responses. Recent studies have uncovered its involvement in host defense against infections, suggesting potential therapeutic applications.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Srinivasan Ramakrishnan, Rodrigo P. Baptista, Beejan Asady, Guozhong Huang, Roberto Docampo
Summary: In Trypanosoma brucei, down-regulation of Vps41 expression through RNAi leads to significant inhibition of endocytosis, affecting cell growth, while other functions of Vps41 in mammalian and yeast cells remain unaffected. The essentiality of TbVps41 suggests it as a potential drug target.
Article
Chemistry, Multidisciplinary
Xinyi Wang, Di Zhang, Ning Jiang, Xiaofeng Wang, Naiwen Zhang, Kai Zhang, Xiaoyu Sang, Ying Feng, Ran Chen, Na Yang, Qijun Chen
Summary: This study investigated the endocytosis of two noble metal nanoclusters in Trypanosoma brucei, highlighting their potential for anti-parasitic treatment. The results showed that the nanoclusters could be efficiently up-taken by T. brucei via a clathrin-dependent endocytosis pathway. The study also revealed that the different nanoclusters interacted with specific organelles and proteins within the parasite, providing insight into the mechanism of action for potential drug development.
Article
Microbiology
Nuria W. Negrao, Logan P. Crowe, Brian S. Mantilla, Rodrigo P. Baptista, Sharon King-Keller, Guozhong Huang, Roberto Docampo
Summary: Trypanosoma brucei is the causative agent of African trypanosomiasis, and there is a need for new drugs due to limited treatment options and evidence of resistance. A phosphoinositide phospholipase C (TbPI-PLC-like) with an X and PDZ domain was discovered, similar to TbPI-PLC1. Recombinant TbPI-PLC-like does not hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) and does not modulate TbPI-PLC1 activity, but its knockdown affects the proliferation of trypanosomes.
Article
Biochemistry & Molecular Biology
Danislav S. Spassov, Mariyana Atanasova, Irini Doytchinova
Summary: N-myristoyltransferase (NMT) inhibitors originally developed for parasitic infections have shown potential as treatments for oncological diseases. A common feature in the inhibitory mechanism of NMT is the formation of a salt bridge between a small molecule's positive chemical group and the enzyme's negative C-terminus. Using virtual screening, we identified several ligands with NMT inhibitory activity, some of which showed promise for further optimization.
Article
Microbiology
Joseph T. Smith Jr, Brianna Tylec, Arunasalam Naguleswaran, Isabel Roditi, Laurie K. Read
Summary: This study reveals the importance of mitochondrial mRNA editing in the developmental regulation of Trypanosoma brucei. The researchers found that temperature reduction and depletion of the differentiation-repressive kinase RDK1 can affect the metabolism of Trypanosoma brucei by altering the editing of mitochondrial cytochrome mRNAs.
Article
Public, Environmental & Occupational Health
Gerardo Priotto, Jose R. Franco, Veerle Lejon, Philippe Buscher, Enock Matovu, Joseph Ndung'u, Sylvain Bieler, Dieudonne Mumba, Nick Van Reet, Paul Verle, Vincent Jamonneau, Pere P. Simarro, Augustin Kadima Ebeja, Dieudonne Sankara, Daniel Argaw Dagne
Summary: Human African trypanosomiasis is a parasitic infection transmitted by the tsetse fly in sub-Saharan Africa. Efforts to eliminate transmission of the disease by 2030 have led to the development of a target product profile for a method to verify the absence of transmission. This method needs to be performed in national or sub-national reference laboratories and have characteristics such as simple specimen collection, no cold-chain requirement, high sensitivity and specificity, high-throughput automated testing, low cost per specimen, and applicability to animals.
BULLETIN OF THE WORLD HEALTH ORGANIZATION
(2023)
Article
Immunology
Yiwei Xie, Hongrui Liang, Ning Jiang, Dingyuan Liu, Naiwen Zhang, Qilong Li, Kai Zhang, Xiaoyu Sang, Ying Feng, Ran Chen, Yiwei Zhang, Qijun Chen
Summary: This study systematically investigated the effect of graphene quantum dots (GQDs) on the pathogen causing African sleeping sickness and revealed the underlying mechanisms. GQDs can be efficiently endocytosed by the parasite, triggering a cascade of apoptotic reactions and inhibiting the enzymatic activity of proteins associated with apoptosis and anti-oxidation responses, ultimately leading to parasite apoptotic death.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Yu Wang, Ranxun Lin, Mengxin Liu, Sen Wang, Hongyu Chen, Wanlin Zeng, Xinyi Nie, Shihua Wang
Summary: As an opportunistic pathogen, A. flavus causes crop loss due to fungal growth and mycotoxin contamination. Investigating the role of virulence factors during infection and searching for novel drug targets have been popular scientific topics in the field of fungal control. Nmt has become a potential target in some organisms.
MICROBIOLOGY SPECTRUM
(2023)
Article
Chemistry, Medicinal
Zezhong Li, Weixiang Xin, Qing Wang, Mingyan Zhu, Huchen Zhou
Summary: New amide compounds were synthesized as inhibitors of T. brucei LeuRS, with compound 74 and 91 showing the highest potency among the series. These compounds represent a new scaffold and potential lead compounds for further development of antitrypanosomal agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Public, Environmental & Occupational Health
Gerardo Priotto, Jose R. Franco, Veerle Lejon, Philippe Buescher, Enock Matovu, Joseph Ndung'u, Sylvain Bieler, Dieudonne Mumba, Nick Van Reet, Paul Verle, Vincent Jamonneau, Pere P. Simarro, Augustin Kadima Ebeja, Dieudonne Sankara, Daniel Argaw Dagne
Summary: Rhodesiense human African trypanosomiasis is a lethal parasitic infection caused by Trypanosoma brucei rhodesiense and transmitted by tsetse flies in eastern and southern Africa. It accounts for approximately 5% of all cases of human African trypanosomiasis. Currently, there is no simple serological test for rhodesiense human African trypanosomiasis and diagnosis relies on microscopic confirmation of trypanosomes in samples of blood or other tissues.
BULLETIN OF THE WORLD HEALTH ORGANIZATION
(2023)
Article
Public, Environmental & Occupational Health
Gerardo Priotto, Jose R. Franco, Veerle Lejon, Philippe Buscher, Enock Matovu, Joseph Ndung'u, Sylvain Bieler, Dieudonne Mumba, Nick Van Reet, Paul Verle, Vincent Jamonneau, Pere P. Simarro, Augustin Kadima Ebeja, Dieudonne Sankara, Daniel Argaw Dagne
Summary: The incidence of human African trypanosomiasis has significantly decreased due to sustained efforts. The World Health Organization has developed a target product profile for assessing T. b. gambiense infection in low-prevalence settings. The profile includes characteristics such as minimal invasiveness, good sensitivity, and long-term stability.
BULLETIN OF THE WORLD HEALTH ORGANIZATION
(2023)
Article
Infectious Diseases
Maria Lucia Sampaio Guther, Alan R. Prescott, Sabine Kuettel, Michele Tinti, Michael A. J. Ferguson
Summary: In Trypanosoma brucei, all nucleotide sugar biosynthesis is compartmentalized to the glycosomes in both lifecycle stages, unlike other eukaryotes. The study identifies the specific enzymatic biotransformations involved in this process and notes the heterogeneity of glycosome contents.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Chemistry, Medicinal
Hamzav Hameed, Elizabeth F. B. King, Katerina Doleckova, Barbara Bartholomew, Jackie Hollinshead, Haddijatou Mbye, Imran Ullah, Karen Walker, Maria Van Veelen, Somaia Saif Abou-Akkada, Robert J. Nash, Paul D. Horrocks, Helen P. Price
Summary: This study screened a library of purified compounds from temperate zone plants against tropical parasitic diseases, identifying potential candidates with significant inhibitory effects on specific parasites.
Article
Multidisciplinary Sciences
Zhe Ji, Michele Tinti, Michael A. J. Ferguson
Summary: The study identified the complex and subunits associated with GPI anchor biosynthesis in Trypanosoma brucei, and revealed the composition and interactions of these proteins through immunoprecipitation and proteomics analysis.
Article
Biochemistry & Molecular Biology
Aurelio Jenni, Sebastian Kueser, Rupa Nagar, Mattias Benninger, Robert Haenel, Michael A. J. Ferguson, Isabel Roditi, Anant K. Menon, Peter Buetikofer
Summary: Studies have shown that TbGPI2 plays an important role in the GPI structure and biosynthesis in trypanosomes, with its absence leading to reduced GPI GlcNAc transferase activity, affected architecture of the GPI GlcNAc transferase complex, and underglycosylation of GPI anchors of major surface proteins. In addition to its expected function as a subunit of the GPI GlcNAc transferase complex, TbGPI2 may have an enigmatic noncanonical role in Golgi-localized GPI anchor modification in trypanosomes, as suggested by immunofluorescence microscopy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Hongjie Guo, Sebastian Damerow, Luciana Penha, Stefanie Menzies, Gloria Polanco, Hicham Zegzouti, Michael A. J. Ferguson, Stephen M. Beverley
Summary: This study identified a mitochondrial fucosyltransferase, FUT1, in the trypanosomatid parasite Leishmania, which is essential for cell viability. The enzyme showed a broad fucosyltransferase activity and its mitochondrial localization was crucial for normal growth and mitochondrial function. Mitochondrial FUT1s in trypanosomatids may be used to study mitochondrial glycosylation and could be a potential target for chemotherapy against these serious human pathogens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Public, Environmental & Occupational Health
Kay Polidano, Linda Parton, Suneth B. Agampodi, Thilini C. Agampodi, Binega H. Haileselassie, Jayasundara M. G. Lalani, Clarice Mota, Helen P. Price, Steffane Rodrigues, Getachew R. Tafere, Leny A. B. Trad, Zenawi Zerihun, Lisa Dikomitis
Summary: This paper discusses the decolonial community engagement model in the ECLIPSE global health research program and presents the implementation of the program in Brazil, Ethiopia, and Sri Lanka. The data collected through qualitative research methods revealed four main themes: establishing community advisory groups, membership and representation, culturally appropriate engagement, and relationships between researchers and community members. The evaluation highlighted a gap between the available community engagement frameworks in literature and the practical realities of working in low-resourced communities.
FRONTIERS IN PUBLIC HEALTH
(2022)
Review
Chemistry, Multidisciplinary
Ernest Man, Helen P. Price, Clare Hoskins
Summary: Cutaneous parasites can be treated with drugs or non-drug strategies, but the increasing resistance requires the development of non-drug approaches. Different cutaneous parasites require specific treatment methods. Developing a comprehensive strategy for cutaneous parasites can save time for diagnosis and treatment.
PHARMACEUTICAL RESEARCH
(2022)
Article
Microbiology
Adam Roberts, Rupa Nagar, Cordelia Brandt, Katherine Harcourt, Simon Clare, Michael A. J. Ferguson, Gavin J. Wright
Summary: This study identified the noncatalytic subunit LdPBN1 of the L. donovani GPI-mannosyltransferase I (GPI-MT I) complex and demonstrated its essentiality for infection in a murine model of visceral leishmaniasis. The LdPBN1 mutant showed potential as an attenuated live vaccine.
Review
Microbiology
Sonali Dinushika Gunasekara, Hasara Nuwangi, Nuwan Darshana Wickramasinghe, Kosala Weerakoon, Helen P. Price, Lisa Dikomitis, Suneth Buddhika Agampodi
Summary: This study reviewed the latest literature on leishmaniasis surveillance in Sri Lanka, and found that Sri Lanka has a well-established surveillance system, but there is room for improvement.
Correction
Multidisciplinary Sciences
Susan Wyllie, Michael Thomas, Stephen Patterson, Sabrinia Crouch, Manu De Rycker, Rhiannon Lowe, Stephanie Gresham, Michael D. Urbaniak, Thomas D. Otto, Laste Stojanovski, Frederick R. C. Simeons, Sujatha Manthri, Lorna M. MacLean, Fabio Zuccotto, Nadine Homeyer, Hannah Pflaumer, Markus Boesche, Lalitha Sastry, Paul Connolly, Sebastian Albrecht, Matt Berriman, Gerard Drewes, David W. Gray, Sonja Ghidelli-Disse, Susan Dixon, Jose M. Fiandor, Paul G. Wyatt, Michael A. J. Ferguson, Alan H. Fairlamb, Timothy J. Miles, Kevin D. Read, Ian H. Gilbert
Article
Biochemistry & Molecular Biology
Rupa Nagar, Isobel Hambleton, Michele Tinti, Mark Carrington, Michael A. J. Ferguson
Summary: In this study, the surface glycoconjugates of T. theileri were purified and partially characterized using biochemical and mass spectrometry-based approaches. It was found that the surface glycoconjugates consist of glycoproteins and glycolipids, including MSPs and TTPSPs. Furthermore, the glycolipids of T. theileri were shown to be larger and more diverse than those of its phylogenetic relative T. cruzi.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jose Carlos Paredes Franco, Maria Lucia Sampaio Guther, Marta L. Lima, Michael A. J. Ferguson
Summary: This study demonstrates the overexpression and enzymatic activity of TcFUT1 in T. cruzi, showing its strict substrate specificity. Furthermore, it confirms the mitochondrial localization of TcFUT1 and suggests a conserved function among trypanosomatids' FUT1 gene products with potential therapeutic targets.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2023)
Review
Social Sciences, Interdisciplinary
Kay Polidano, Brianne Wenning, Alejandra Ruiz-Cadavid, Baheya Dawaishan, Jay Panchal, Sonali Gunasekara, Haftom Abebe, Marciglei Morais, Helen Price, Lisa Dikomitis
Summary: This article reviews the evidence on community-based interventions for the prevention and control of cutaneous leishmaniasis (CL). The findings suggest that educational interventions can improve people's knowledge, attitudes, and practices about CL, but it is argued that this approach alone is insufficient for the prevention and control of the disease. More innovative community-based interventions focusing on broader issues such as stigma, financial barriers, and healthcare access are recommended.
SOCIAL SCIENCES-BASEL
(2022)
Article
Public, Environmental & Occupational Health
Brianne Wenning, Helen Price, Hasara Nuwangi, Kelemework Tafere Reda, Ben Walters, Reem Ehsanullah, Greice Viana, Alina Andras, Lisa Dikomitis
Summary: This review examines existing studies on the impact of gender on cutaneous leishmaniasis. The results show that gender plays a significant role in health-seeking behaviors, treatment choices, stigma, and scarring. Women experience more constraints in seeking healthcare and face greater stigma, while men are more at risk of infection and may resort to harmful self-treatments. The authors recommend that future research considers the influence of gender on the experiences of individuals.
GLOBAL HEALTH RESEARCH AND POLICY
(2022)
Article
Biochemistry & Molecular Biology
Luciana S. Paradela, Richard J. Wall, Sandra Carvalho, Giulia Chemi, Victoriano Corpas-Lopez, Eoin Moynihan, Davide Bello, Stephen Patterson, Maria Lucia S. Guther, Alan H. Fairlamb, Michael A. J. Ferguson, Fabio Zuccotto, Julio Martin, Ian H. Gilbert, Susan Wyllie
Summary: A benzothiophene compound with activity against Leishmania donovani was found, with oxidosqualene cyclase (OSC) identified as its target. The amplification of the OSC gene was associated with resistance to the compound, and introduction of an ectopic copy of the gene reduced susceptibility. Biochemical analyses showed substrate accumulation and product depletion in cells treated with the compound, confirming direct binding of the compound to OSC.
CELL CHEMICAL BIOLOGY
(2021)
