Article
Microbiology
Elizabeth Gyamfi, Magdalene Amerl Dogbe, Charles Quaye, Abel Adjet Affouda, Edwin Kyei-Baffour, Daisy Awuku-Asante, Mabel Sarpong-Duah, Lydia Mosi
Summary: This study aimed to identify genetic differences among Mycobacterium ulcerans strains between two Buruli ulcer endemic countries, Ghana and Cote d'Ivoire. The study found different genotypes among clinical and environmental samples, with clinical isolates showing more heterogeneity. Genotype D was found to be prominent in both clinical and environmental samples, suggesting possible transmission of M. ulcerans from the environment to humans.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Laxmi Dhungel, Raisa Bonner, Meagan Cook, Duncan Henson, Trent Moulder, M. Eric Benbow, Heather Jordan
Summary: Buruli ulcer disease is caused by the pathogen Mycobacterium ulcerans and is characterized by tissue necrosis and ulceration. In this study, the modulation of mycolactone and other genes in response to changing UV and oxygen levels was investigated. The data showed that the expression of mycolactone was influenced by temperature and oxygen levels, providing insight into the metabolic responses of the pathogen.
MICROBIOLOGY SPECTRUM
(2023)
Article
Immunology
Belinda S. Hall, Louise Tzung-Harn Hsieh, Sandra Sacre, Rachel E. Simmonds
Summary: Buruli ulcer is a devastating skin disease caused by Mycobacterium ulcerans, with its pathogenesis involving the exotoxin mycolactone that suppresses the immune system and is cytotoxic. Despite immune blockade, evidence suggests that IL-1 beta production is possible, shedding light on potential treatments for the disease.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
B. G. O. Tchan, S. Ngazoa-Kakou, N. Aka, N. K. B. Apia, N. Hammoudi, M. Drancourt, J. Saad
Summary: We describe a new targeted sequencing approach that characterizes the PPE gene to disclose the simultaneous presence of different variants of a single pathogenic microorganism. This has direct implications on understanding pathogen diversity and natural history and therapeutic implications when dealing with obligate and opportunistic pathogens. By establishing a comprehensive database and utilizing PPE gene sequencing, the identification and typing of clinical M. ulcerans strains can be done more efficiently.
MICROBIOLOGY SPECTRUM
(2023)
Article
Public, Environmental & Occupational Health
Laxmi Dhungel, Mark Eric Benbow, Heather Rose Jordan
Summary: Buruli ulcer, caused by Mycobacterium ulcerans, is a challenging necrotizing skin disease in West Africa due to unknown transmission modes and occurrence in remote areas. A One Health approach is needed to advance understanding of transmission and design management strategies. Understanding bacterial ecology, environmental niches, and the role of mycolactone is crucial in preventing and responding to this mysterious disease.
Review
Immunology
Caroline Demangel
Summary: This article explores the Buruli ulcer disease caused by Mycobacterium ulcerans, focusing on the impact of mycolactone on the immune system and potential therapeutic strategies.
IMMUNOLOGICAL REVIEWS
(2021)
Article
Immunology
Emily Strong, Bryan Hart, Jia Wang, Maria Gonzalez Orozco, Sunhee Lee
Summary: Mycobacterium ulcerans is the causative agent of Buruli ulcer, secreting mycolactone which affects the intracellular environment. A new inducible system has been developed to study the role of mycolactone during M. ulcerans infection in more detail.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Infectious Diseases
Ronald Gnimavo, Alban Besnard, Horace Degnonvi, Juliana Pipoli Da Fonseca, Marie Kempf, Christian Roch Johnson, Alexandra Boccarossa, Yao Telesphore Brou, Laurent Marsollier, Estelle Marion
Summary: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, with the main risk factor being living near contaminated water sources. This study identified two cases of Buruli ulcer recurrence due to reinfection with M. ulcerans through DNA comparison, indicating a non-random distribution of M. ulcerans genotypes in the region.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Microbiology
Juan Dominguez, Ana I. Mendes, Ana R. Pacheco, Maria J. Peixoto, Jorge Pedrosa, Alexandra G. Fraga
Summary: Buruli Ulcer is a common infectious skin disease that can cause severe disfigurement and disability if not treated in a timely manner. The standard antibiotic regimen for treatment has limitations, leading researchers to explore new drug candidates. This study found that statins have the potential to be effective in treating Buruli Ulcer.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Philippe Bahadoran, Nassim Hammoudi, Alice Gaudart, Jamal Saad, Yoan Di Filippo, Michel Drancourt, Raymond Ruimy
Summary: This report describes a case of Buruli ulcer in a peri-urban area in Cote d'Ivoire, confirmed by whole genome sequencing to be caused by a Mycobacterium ulcerans genotype not previously reported in Cote d'Ivoire.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2021)
Article
Immunology
Melanie Foulon, Marie Robbe-Saule, Lucille Esnault, Marine Malloci, Anthony Mery, Jean-Paul Saint-Andre, Anne Croue, Marie Kempf, Chadi Homedan, Estelle Marion, Laurent Marsollier
Summary: This study found that a ketogenic diet can prevent the formation of Buruli ulcer by modulating bacterial growth and host inflammatory response.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Immunology
Laure F. Pittet, Marc Tebruegge, Binita Dutta, Susan Donath, Nicole Messina, Dan Casalaz, Willem A. Hanekom, Warwick J. Britton, Roy Robins-Browne, Nigel Curtis, Nicole Ritz
Summary: BCG vaccination induces M. ulcerans-specific immune responses in infants, likely explaining the cross-protective effect observed in epidemiological studies. These immune responses show similar patterns to those observed in M. tuberculosis-stimulated samples.
Article
Biology
Koen Vandelannoote, Andrew H. Buultjens, Jessica L. Porter, Anita Velink, John R. Wallace, Kim R. Blasdell, Michael Dunn, Victoria Boyd, Janet A. M. Fyfe, Ee Laine Tay, Paul D. R. Johnson, Saras M. Windecker, Nick Golding, Timothy P. Stinear
Summary: This study establishes a model based on possum excreta surveillance that can effectively predict the occurrence of human BU cases and guide public health interventions.
Article
Pharmacology & Pharmacy
Bruno Tello Rubio, Florence Bugault, Blandine Baudon, Bertrand Raynal, Sebastien Brule, Jean-David Morel, Sarah Saint-Auret, Nicolas Blanchard, Caroline Demangel, Laure Guenin-Mace
Summary: Mycolactone specifically associates with serum albumin and lipoproteins for solubilization, regulating its bioavailability, while Scavenger Receptor (SR)-B1 contributes to its cellular uptake, suggesting a new mechanism of transport and cell entry.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Dongmin J. Kim, Tawni K. Crippen, Laxmi R. Dhungel, Pablo Delclos, Jeffery Tomberlin, Heather Jordan
Summary: This study found that mosquitoes are more attracted to MU that produces Mycolactone than to MUlac-, and MU enhances the expression of Mycolactone when in contact with mosquitoes, resulting in differential volatile organic compounds. These findings elucidate the interkingdom interactions between viable M. ulcerans bacteria and Ae. aegypti mosquitoes, opening new doors for future research.
Article
Biochemistry & Molecular Biology
Anja Nylander, Pawel Leznicki, Karina Vidovic, Stephen High, Martin L. Olsson
BIOSCIENCE REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Pawel Leznicki, Stephen High
Editorial Material
Biochemistry & Molecular Biology
Sarah O'Keefe, Stephen High
Article
Biochemistry & Molecular Biology
Samuel F. Gerard, Belinda S. Hall, Afroditi M. Zaki, Katherine A. Corfield, Peter U. Mayerhofer, Catia Costa, Daniel K. Whelligan, Philip C. Biggin, Rachel E. Simmonds, Matthew K. Higgins
Article
Biochemistry & Molecular Biology
Maurice Steenhuis, Gregory M. Koningstein, Julia Oswald, Tillman Pick, Sarah O'Keefe, Hans-Georg Koch, Adolfo Cavalie, Roger C. Whitehead, Eileithyia Swanton, Stephen High, Joen Luirink
Summary: ES24 is an inhibitor that affects bacterial protein secretion and insertion by targeting the SecYEG translocon. This compound has a complex mode of action, potentially involving multiple targets, and exhibits antibacterial activity which requires activation by nitroreductases.
MOLECULAR MICROBIOLOGY
(2021)
Article
Cell Biology
Sarah O'Keefe, Peristera Roboti, Kwabena B. Duah, Guanghui Zong, Hayden Schneider, Wei Q. Shi, Stephen High
Summary: The study found that the small molecule inhibitor Ipom-F can effectively block the synthesis of SARS-CoV-2 infection proteins to reduce pathogenicity, suggesting a new strategy for antiviral drugs.
JOURNAL OF CELL SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Sarah O'Keefe, Martin R. Pool, Stephen High
Summary: The Sec61 complex in the ER plays a central role in protein translocation, recruiting accessory complexes and coordinating the co-translational insertion of proteins. Some transmembrane proteins preferentially utilize alternative pathways for insertion. Our understanding of post-insertion events has improved, with embedded chaperone complexes aiding in the assembly of multi-span proteins.
Article
Cell Biology
Belinda S. Hall, Scott J. Dos Santos, Louise Tzung-Harn Hsieh, Maria Manifava, Marie-Therese Ruf, Gerd Pluschke, Nicholas Ktistakis, Rachel E. Simmonds
Summary: Mycolactone inhibits SEC61-dependent co-translational translocation of proteins into the endoplasmic reticulum and activates multiple EIF2S1/eIF2 alpha kinases, leading to increased initiation of autophagy. Autophagic response to mycolactone is regulated by translational regulation by EIF2S1 in the integrated stress response.
Article
Cell Biology
Pawel Leznicki, Hayden O. Schneider, Jada Harvey, Wei Q. Shi, Stephen High
Summary: Membrane proteins destined for lipid droplets can be delivered to the endoplasmic reticulum either co- or post-translationally. The co-translational pathway relies on the ER membrane protein complex for membrane insertion, and may result in structural rearrangements.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biology
Sarah O'Keefe, Guanghui Zong, Kwabena B. Duah, Lauren E. Andrews, Wei Q. Shi, Stephen High
Summary: The integration of type III single-pass transmembrane proteins targeted to the ER and the roles of the ER membrane complex, Sec61 complex and signal recognition particle receptor were investigated by O'Keefe et al. The authors proposed an alternative mechanism of insertion, reconciling the ability of type III transmembrane proteins to bypass an ipomoeassin-F-mediated blockade of membrane integration.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Peristera Roboti, Craig Lawless, Stephen High
Summary: The heterotrimeric BAG6 complex plays a role in coordinating the transport of newly synthesised membrane proteins and processing defective precursors. It also interacts with the mitochondrial antiviral-signalling protein MAVS and regulates its role in the cellular response to viral infection.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Sarah O'Keefe, Pratiti Bhadra, Kwabena B. Duah, Guanghui Zong, Levise Tenay, Lauren Andrews, Hayden Schneider, Ashley Anderson, Zhijian Hu, Hazim S. Aljewari, Belinda S. Hall, Rachel E. Simmonds, Volkhard Helms, Stephen High, Wei Q. Shi
Summary: This study demonstrates that macrocyclic integrity is not necessary for the cytotoxic inhibition of Sec61-dependent protein translocation by Ipom-F. The researchers find that open-chain analogues can interact with multiple sites on the Sec61 alpha subunit. Additionally, they discover a stereochemically simplified analogue that is more potent and easier to synthesize.
Article
Cell Biology
Andrea Tirincsi, Sarah O'Keefe, Duy Nguyen, Mark Sicking, Johanna Dudek, Friedrich Forster, Martin Jung, Drazena Hadzibeganovic, Volkhard Helms, Stephen High, Richard Zimmermann, Sven Lang
Summary: Importing proteins into the endoplasmic reticulum is crucial for approximately 30% of the human proteome, involving precursor protein targeting and insertion or translocation across the ER membrane with the help of signals in precursor polypeptides. Little is known about the SRP-independent/SND pathway, and our study aimed to identify additional components and characterize the client spectrum of this pathway, finding that SND clients are predominantly membrane proteins.
Biographical-Item
Biochemistry & Molecular Biology
Ineke Braakman, Stephen High, Karl Kadler, Roberto Sitia, Kostas Tokatlidis, Philip Woodman
Article
Multidisciplinary Sciences
Michael J. McKenna, Sue Im Sim, Alban Ordureau, Lianjie Wei, J. Wade Harper, Sichen Shao, Eunyong Park