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Laurent Marsollier - One of the best experts on this subject based on the ideXlab platform.
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ketogenic diet impairs Mycobacterium ulcerans growth and toxin production enhancing hosts response to the infection in an experimental mouse model
The Journal of Infectious Diseases, 2021Co-Authors: Melanie Foulon, Estelle Marion, Marie Robbesaule, Lucille Esnault, Marine Malloci, Anthony Mery, Jeanpaul Saintandre, Marie Kempf, Chadi Homedan, Laurent MarsollierAbstract:Ketogenic diets have been used to treat diverse conditions, and there is growing evidence of their benefits for tissue repair and in inflammatory disease treatment. However, their role in infectious diseases has been little studied. Buruli ulcer (Mycobacterium ulcerans infection) is a chronic infectious disease characterized by large skin ulcerations caused by mycolactone, the major virulence factor of the bacillus. Here, we investigated the impact of ketogenic diet on this cutaneous disease in an experimental mouse model. This diet prevented ulceration, by modulating bacterial growth and host inflammatory response. β-hydroxybutyrate, the major ketone body produced during ketogenic diet and diffusing in tissues, impeded M. ulcerans growth and mycolactone production in vitro underlying its potential key role in infection. These results pave the way for the development of new patient management strategies involving shorter courses of treatment and improving wound healing, in line with the major objectives of the World Health Organization.
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Ecology and Feeding Habits Drive Infection of Water Bugs with Mycobacterium ulcerans
EcoHealth, 2017Co-Authors: Solange Meyin A. Ebong, Sara Eyangoh, Dominique Pluot-sigwalt, Gabriel E. García-peña, Laurent Marsollier, Philippe Gall, Jean-françois GueganAbstract:Mycobacterium ulcerans (MU), the causative agent of Buruli ulcer, is present in a wide spectrum of environments, including terrestrial and aquatic ecosystems in tropical regions. The most promising studies on the epidemiological risk of this disease suggest that some ecological settings may favor infection of animals with MU including human. A species’ needs and impacts on resources and the environment, i.e., its ecological niche, may influence its susceptibility to be infected by this microbial form. For example, some Naucoridae may dive in fresh waters to prey upon infected animals and thus may get infected with MU. However, these studies have rarely considered that inference on the ecological settings favoring infection and transmission may be confounded because host carrier sister species have similar ecological niches, and potentially the same host–microbe interactions. Hence, a relationship between the ecological niche of Naucoridae and its infection with MU may be due to a symbiotic relationship between the host and the pathogen, rather than its ecological niche. To account for this confounding effect, we investigated the relationships between surrogates of the ecological niche of water bug species and their susceptibility to MU, by performing phylogenetic comparative analyses on a large dataset of 11 families of water bugs collected in 10 different sites across Cameroon, central Africa. Our results indicate that MU circulates and infects a couple of host taxa, i.e., Belostomatidae, Naucoridae, living both in the aquatic vegetation and as predators inside the trophic network and sister species of water bugs have indeed similar host–microbe interactions with MU.
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Chitin promotes Mycobacterium ulcerans growth
FEMS Microbiology Ecology, 2016Co-Authors: Daniel Sanhueza, Laurent Marsollier, Christine Chevillon, Rita Colwell, Jérémie Babonneau, Estelle Marion, Jean-françois GueganAbstract:† Equally contributed as co-supervisors of this work One sentence summary: Chitin increased Mycobacterium ulcerans (MU) growth significantly providing a nutrient source or environmental support for the bacillus, thereby, providing a focus on the association between MU and aquatic arthropods. ABSTRACT Mycobacterium ulcerans (MU) is the causative agent of Buruli ulcer, an emerging human infectious disease. However, both the ecology and life cycle of MU are poorly understood. The occurrence of MU has been linked to the aquatic environment, notably water bodies affected by human activities. It has been hypothesized that one or a combination of environmental factor(s) connected to human activities could favour growth of MU in aquatic systems. Here, we tested in vitro the growth effect of two ubiquitous polysaccharides and five chemical components on MU at concentration ranges shown to occur in endemic regions. Real-time PCR showed that chitin increased MU growth significantly providing a nutrient source or environmental support for the bacillus, thereby, providing a focus on the association between MU and aquatic arthropods. Aquatic environments with elevated population of arthropods provide increased chitin availability and, thereby, enhanced multiplication of MU. If calcium very slightly enhanced MU growth, iron, zinc, sulphate and phosphate did not stimulate MU growth, and at the concentration ranges of this study would limit MU population in natural ecosystems. 20 25
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Mycobacterium ulcerans dynamics in aquatic ecosystems are driven by a complex interplay of abiotic and biotic factors
eLife, 2015Co-Authors: Andres Garchitorena, Sara Eyangoh, Jean-françois Guegan, Laurent Marsollier, Lucas Léger, Benjamin RocheAbstract:Host–parasite interactions are often embedded within complex host communities and can be influenced by a variety of environmental factors, such as seasonal variations in climate or abiotic conditions in water and soil, which confounds our understanding of the main drivers of many multi-host pathogens. Here, we take advantage of a combination of large environmental data sets on Mycobacterium ulcerans (MU), an environmentally persistent microorganism associated to freshwater ecosystems and present in a large variety of aquatic hosts, to characterize abiotic and biotic factors driving the dynamics of this pathogen in two regions of Cameroon. We find that MU dynamics are largely driven by seasonal climatic factors and certain physico-chemical conditions in stagnant and slow-flowing ecosystems, with an important role of pH as limiting factor. Furthermore, water conditions can modify the effect of abundance and diversity of aquatic organisms on MU dynamics, which suggests a different contribution of two MU transmission routes for aquatic hosts (trophic vs environmental transmission) depending on local abiotic factors. DOI: http://dx.doi.org/10.7554/eLife.07616.001
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comprehensive proteome analysis of Mycobacterium ulcerans and quantitative comparison of mycolactone biosynthesis
Proteomics, 2008Co-Authors: Petra Tafelmeyer, Laurent Marsollier, Christine Laurent, Pascal Lenormand, Jeanclaude Rousselle, Gilles Reysset, Runxuan Zhang, Albert Sickmann, Timothy P. StinearAbstract:Mycobacterium ulcerans is the causative agent of Buruli ulcer, a rapidly emerging human disease in which mycolactone, a cytotoxic and immunosuppressive macrocyclic polyketide, is responsible for massive skin destruction. The genome sequencing of M. ulcerans has recently been accomplished (http://genolist.pasteur.fr/BuruList/) enabling the first proteome study of this important human pathogen. Here, we present a comprehensive proteome analysis of different subcellular fractions and culture supernatant of in vitro grown M. ulcerans. By a combination of gel-based and gel-free techniques for protein and peptide separation with subsequent analysis by MS, we identified 1074 different proteins, corresponding to 25% of the protein-coding DNA sequence. Interestingly, new information was obtained about central metabolism and lipid biosynthesis, and as many as 192 conserved hypothetical proteins were found. Comparative analysis of the wild-type strain and an isogenic mycolactone-deficient mutant, by 2-DE and iTRAQ labeling of the cytoplasmic fraction, revealed differences in the expression profiles of proteins involved in lipid metabolism and information pathways, as well as stress responses.
Francoise Portaels - One of the best experts on this subject based on the ideXlab platform.
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Mycobacterium ulcerans population genomics to inform on the spread of buruli ulcer across central africa
mSphere, 2019Co-Authors: Koen Vandelannoote, Conor J Meehan, Miriam Eddyani, Delphin Mavinga Phanzu, Kapay Kibadi, Francoise Portaels, Kurt Jordaens, Herwig Leirs, Timothy P. StinearAbstract:ABSTRACT Buruli ulcer is a neglected tropical disease of skin and subcutaneous tissue caused by infection with the pathogen Mycobacterium ulcerans. Many critical issues for disease control, such as understanding the mode of transmission and identifying source reservoirs of M. ulcerans, are still largely unknown. Here, we used genomics to reconstruct in detail the evolutionary trajectory and dynamics of M. ulcerans populations at a central African scale and at smaller geographical village scales. Whole-genome sequencing (WGS) data were analyzed from 179 M. ulcerans strains isolated from all Buruli ulcer foci in the Democratic Republic of the Congo, The Republic of Congo, and Angola that have ever yielded positive M. ulcerans cultures. We used both temporal associations and the study of the mycobacterial demographic history to estimate the contribution of humans as a reservoir in Buruli ulcer transmission. Our phylogeographic analysis revealed one almost exclusively predominant sublineage of M. ulcerans that arose in Central Africa and proliferated in its different regions of endemicity during the Age of Discovery. We observed how the best sampled endemic hot spot, the Songololo territory, became an area of endemicity while the region was being colonized by Belgium (1880s). We furthermore identified temporal parallels between the observed past population fluxes of M. ulcerans from the Songololo territory and the timing of health policy changes toward control of the Buruli ulcer epidemic in that region. These findings suggest that an intervention based on detecting and treating human cases in an area of endemicity might be sufficient to break disease transmission chains, irrespective of other reservoirs of the bacterium. IMPORTANCE Buruli ulcer is a destructive skin and soft tissue infection caused by Mycobacterium ulcerans. The disease is characterized by progressive skin ulceration, which can lead to permanent disfigurement and long-term disability. Currently, the major hurdles facing disease control are incomplete understandings of both the mode of transmission and environmental reservoirs of M. ulcerans. As decades of spasmodic environmental sampling surveys have not brought us much closer to overcoming these hurdles, the Buruli ulcer research community has recently switched to using comparative genomics. The significance of our research is in how we used both temporal associations and the study of the mycobacterial demographic history to estimate the contribution of humans as a reservoir in Buruli ulcer transmission. Our approach shows that it might be possible to use bacterial population genomics to assess the impact of health interventions, providing valuable feedback for managers of disease control programs in areas where health surveillance infrastructure is poor.
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Mycobacterium ulcerans Population Genomics To Inform on the Spread of Buruli Ulcer across Central Africa
American Society for Microbiology, 2019Co-Authors: Koen Vandelannoote, Conor J Meehan, Miriam Eddyani, Delphin Mavinga Phanzu, Kapay Kibadi, Timothy P. Stinear, Francoise Portaels, Kurt Jordaens, Herwig Leirs, Simon R. HarrisAbstract:Buruli ulcer is a destructive skin and soft tissue infection caused by Mycobacterium ulcerans. The disease is characterized by progressive skin ulceration, which can lead to permanent disfigurement and long-term disability. Currently, the major hurdles facing disease control are incomplete understandings of both the mode of transmission and environmental reservoirs of M. ulcerans. As decades of spasmodic environmental sampling surveys have not brought us much closer to overcoming these hurdles, the Buruli ulcer research community has recently switched to using comparative genomics. The significance of our research is in how we used both temporal associations and the study of the mycobacterial demographic history to estimate the contribution of humans as a reservoir in Buruli ulcer transmission. Our approach shows that it might be possible to use bacterial population genomics to assess the impact of health interventions, providing valuable feedback for managers of disease control programs in areas where health surveillance infrastructure is poor.Buruli ulcer is a neglected tropical disease of skin and subcutaneous tissue caused by infection with the pathogen Mycobacterium ulcerans. Many critical issues for disease control, such as understanding the mode of transmission and identifying source reservoirs of M. ulcerans, are still largely unknown. Here, we used genomics to reconstruct in detail the evolutionary trajectory and dynamics of M. ulcerans populations at a central African scale and at smaller geographical village scales. Whole-genome sequencing (WGS) data were analyzed from 179 M. ulcerans strains isolated from all Buruli ulcer foci in the Democratic Republic of the Congo, The Republic of Congo, and Angola that have ever yielded positive M. ulcerans cultures. We used both temporal associations and the study of the mycobacterial demographic history to estimate the contribution of humans as a reservoir in Buruli ulcer transmission. Our phylogeographic analysis revealed one almost exclusively predominant sublineage of M. ulcerans that arose in Central Africa and proliferated in its different regions of endemicity during the Age of Discovery. We observed how the best sampled endemic hot spot, the Songololo territory, became an area of endemicity while the region was being colonized by Belgium (1880s). We furthermore identified temporal parallels between the observed past population fluxes of M. ulcerans from the Songololo territory and the timing of health policy changes toward control of the Buruli ulcer epidemic in that region. These findings suggest that an intervention based on detecting and treating human cases in an area of endemicity might be sufficient to break disease transmission chains, irrespective of other reservoirs of the bacterium
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Short Report: Edematous Mycobacterium ulcerans Infection (Buruli Ulcer) on the Face: A Case Report
2015Co-Authors: Delphin Mavinga Phanzu, Desire Bofunga B Imposo, Patrick Suykerbuyk, Wayne M Meyers, Anthony Ablordey, Lucien Lefevre, Roger L. Mahema, Francoise PortaelsAbstract:Abstract. We report a case of a four-year-old Angolan boy with the edematous form of Buruli ulcer on the face and scalp, who was treated at a rural hospital in the Bas-Congo Province, Democratic Republic of Congo. Treatment consisted of a series of surgical interventions and antimycobacterial chemotherapy (rifampin and ciprofloxacin) for two months. This case demonstrates the diagnostic and management difficulties of an edematous lesion of BU on the face and suggests an enhancement of healing and limitation of extent of excision by specific antibiotherapy. The outcome in this patient also underscores the importance of prompt referral of suspected cases and training of health professionals in the early diagnosis of BU. Buruli ulcer (BU) is a severe disabling and disfiguring dis-ease caused by Mycobacterium ulcerans. Its affects primarily children less than 15 years of age in many tropical and sub-tropical countries.1–3 In early or preulcerative lesions, M. ul-cerans produces a lipid toxin, mycolactone, which is respon-sible for necrosis of the dermis, panniculus, and fascia, culmi-nating in extensive ulcers.4 Preulcerative lesions and small ulcers may be surgically excised and closed. However, anti
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pathogenetic mechanisms of the intracellular parasite Mycobacterium ulcerans leading to buruli ulcer
Lancet Infectious Diseases, 2009Co-Authors: Manuel T Silva, Francoise Portaels, Jorge PedrosaAbstract:The necrotising skin infection Buruli ulcer is at present the third most common human mycobacteriosis worldwide, after tuberculosis and leprosy. Buruli ulcer is an emergent disease that is predominantly found in humid tropical regions. There is no vaccine against Buruli ulcer and its treatment is difficult. In addition to the huge social effect, Buruli ulcer is of great scientific interest because of the unique characteristics of its causative organism, Mycobacterium ulcerans. This pathogen is genetically very close to the typical intracellular parasites Mycobacterium marinum and Mycobacterium tuberculosis. We review data supporting the interpretation that M ulcerans has the essential hallmarks of an intracellular parasite, producing infections associated with immunologically relevant inflammatory responses, cell-mediated immunity, and delayed-type hypersensitivity. This interpretation judges that whereas M ulcerans behaves like the other pathogenic mycobacteria, it represents an extreme in the biodiversity of this family of pathogens because of its higher cytotoxicity due to the secretion of the exotoxin mycolactone. The acceptance of the interpretation that Buruli ulcer is caused by an intracellular parasite has relevant prophylactic and therapeutic implications, rather than representing the mere attribution of a label with academic interest, because it prompts the development of vaccines that boost cell-mediated immunity and the use of chemotherapeutic protocols that include intracellularly active antibiotics.
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buruli ulcer Mycobacterium ulcerans infection
Transactions of The Royal Society of Tropical Medicine and Hygiene, 2008Co-Authors: Douglas S Walsh, Francoise Portaels, Wayne M MeyersAbstract:Mycobacterium ulcerans is an emerging infection that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU). Bone lesions may include reactive osteitis or osteomyelitis beneath skin lesions, or metastatic osteomyelitis from lymphohematogenous spread of M. ulcerans. Pathogenesis is related to a necrotizing and immunosuppressive toxin produced by M. ulcerans, called mycolactone. The incidence of BU is highest in children up to 15 years old, and is a major public health problem in endemic countries due to disabling scarring and destruction of bone. Most patients live in West Africa, but the disease has been confirmed in at least 30 countries. Treatment options for BU are antibiotics and surgery. BCG vaccination provides short-term protection against M. ulcerans infection and prevents osteomyelitis. HIV infection may increase risk for BU, and renders BU highly aggressive. Unlike leprosy and tuberculosis, BU is related to environmental factors and is thus considered non-communicable. The most plausible mode of transmission is by skin trauma at sites contaminated by M. ulcerans. The reemergence of BU around 1980 may be attributable to environmental factors such as deforestation, artificial topographic alterations and increased manual agriculture of wetlands. The first cultivation of M. ulcerans from nature was reported in 2008.
Jean-françois Guegan - One of the best experts on this subject based on the ideXlab platform.
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environmental variations in Mycobacterium ulcerans transcriptome absence of mycolactone expression in suboptimal environments
Toxins, 2019Co-Authors: Daniel Sanhueza, Heather R Jordan, Jean-françois Guegan, Christine ChevillonAbstract:: Buruli ulcer is a neglected tropical infectious disease, produced by the environmentally persistent pathogen Mycobacterium ulcerans (MU). Neither the ecological niche nor the exact mode of transmission of MU are completely elucidated. However, some environmental factors, such as the concentration in chitin and pH values, were reported to promote MU growth in vitro. We pursued this research using next generation sequencing (NGS) and mRNA sequencing to investigate potential changes in MU genomic expression profiles across in vitro environmental conditions known to be suitable for MU growth. Supplementing the growth culture medium in either chitin alone, calcium alone, or in both chitin and calcium significantly impacted the MU transcriptome and thus several metabolic pathways, such as, for instance, those involved in DNA synthesis or cell wall production. By contrast, some genes carried by the virulence plasmid and necessary for the production of the mycolactone toxin were expressed neither in control nor in any modified environments. We hypothesized that these genes are only expressed in stressful conditions. Our results describe important environmental determinants playing a role in the pathogenicity of MU, helping the understanding of its complex natural life cycle and encouraging further research using genomic approaches.
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Ecology and Feeding Habits Drive Infection of Water Bugs with Mycobacterium ulcerans
EcoHealth, 2017Co-Authors: Solange Meyin A. Ebong, Sara Eyangoh, Dominique Pluot-sigwalt, Gabriel E. García-peña, Laurent Marsollier, Philippe Gall, Jean-françois GueganAbstract:Mycobacterium ulcerans (MU), the causative agent of Buruli ulcer, is present in a wide spectrum of environments, including terrestrial and aquatic ecosystems in tropical regions. The most promising studies on the epidemiological risk of this disease suggest that some ecological settings may favor infection of animals with MU including human. A species’ needs and impacts on resources and the environment, i.e., its ecological niche, may influence its susceptibility to be infected by this microbial form. For example, some Naucoridae may dive in fresh waters to prey upon infected animals and thus may get infected with MU. However, these studies have rarely considered that inference on the ecological settings favoring infection and transmission may be confounded because host carrier sister species have similar ecological niches, and potentially the same host–microbe interactions. Hence, a relationship between the ecological niche of Naucoridae and its infection with MU may be due to a symbiotic relationship between the host and the pathogen, rather than its ecological niche. To account for this confounding effect, we investigated the relationships between surrogates of the ecological niche of water bug species and their susceptibility to MU, by performing phylogenetic comparative analyses on a large dataset of 11 families of water bugs collected in 10 different sites across Cameroon, central Africa. Our results indicate that MU circulates and infects a couple of host taxa, i.e., Belostomatidae, Naucoridae, living both in the aquatic vegetation and as predators inside the trophic network and sister species of water bugs have indeed similar host–microbe interactions with MU.
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Chitin promotes Mycobacterium ulcerans growth
FEMS Microbiology Ecology, 2016Co-Authors: Daniel Sanhueza, Laurent Marsollier, Christine Chevillon, Rita Colwell, Jérémie Babonneau, Estelle Marion, Jean-françois GueganAbstract:† Equally contributed as co-supervisors of this work One sentence summary: Chitin increased Mycobacterium ulcerans (MU) growth significantly providing a nutrient source or environmental support for the bacillus, thereby, providing a focus on the association between MU and aquatic arthropods. ABSTRACT Mycobacterium ulcerans (MU) is the causative agent of Buruli ulcer, an emerging human infectious disease. However, both the ecology and life cycle of MU are poorly understood. The occurrence of MU has been linked to the aquatic environment, notably water bodies affected by human activities. It has been hypothesized that one or a combination of environmental factor(s) connected to human activities could favour growth of MU in aquatic systems. Here, we tested in vitro the growth effect of two ubiquitous polysaccharides and five chemical components on MU at concentration ranges shown to occur in endemic regions. Real-time PCR showed that chitin increased MU growth significantly providing a nutrient source or environmental support for the bacillus, thereby, providing a focus on the association between MU and aquatic arthropods. Aquatic environments with elevated population of arthropods provide increased chitin availability and, thereby, enhanced multiplication of MU. If calcium very slightly enhanced MU growth, iron, zinc, sulphate and phosphate did not stimulate MU growth, and at the concentration ranges of this study would limit MU population in natural ecosystems. 20 25
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environmental transmission of Mycobacterium ulcerans drives dynamics of buruli ulcer in endemic regions of cameroon
Scientific Reports, 2015Co-Authors: Sara Eyangoh, Jordi Landier, Calistus N Ngonghala, Andres Garchitorena, Matthew H Bonds, Gaetan Texier, Jean-françois GueganAbstract:Buruli Ulcer is a devastating skin disease caused by the pathogen Mycobacterium ulcerans. Emergence and distribution of Buruli ulcer cases is clearly linked to aquatic ecosystems, but the specific route of transmission of M. ulcerans to humans remains unclear. Relying on the most detailed field data in space and time on M. ulcerans and Buruli ulcer available today, we assess the relative contribution of two potential transmission routes –environmental and water bug transmission– to the dynamics of Buruli ulcer in two endemic regions of Cameroon. The temporal dynamics of Buruli ulcer incidence are explained by estimating rates of different routes of transmission in mathematical models. Independently, we also estimate statistical models of the different transmission pathways on the spatial distribution of Buruli ulcer. The results of these two independent approaches are corroborative and suggest that environmental transmission pathways explain the temporal and spatial patterns of Buruli ulcer in our endemic areas better than the water bug transmission.
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Mycobacterium ulcerans dynamics in aquatic ecosystems are driven by a complex interplay of abiotic and biotic factors
eLife, 2015Co-Authors: Andres Garchitorena, Sara Eyangoh, Jean-françois Guegan, Laurent Marsollier, Lucas Léger, Benjamin RocheAbstract:Host–parasite interactions are often embedded within complex host communities and can be influenced by a variety of environmental factors, such as seasonal variations in climate or abiotic conditions in water and soil, which confounds our understanding of the main drivers of many multi-host pathogens. Here, we take advantage of a combination of large environmental data sets on Mycobacterium ulcerans (MU), an environmentally persistent microorganism associated to freshwater ecosystems and present in a large variety of aquatic hosts, to characterize abiotic and biotic factors driving the dynamics of this pathogen in two regions of Cameroon. We find that MU dynamics are largely driven by seasonal climatic factors and certain physico-chemical conditions in stagnant and slow-flowing ecosystems, with an important role of pH as limiting factor. Furthermore, water conditions can modify the effect of abundance and diversity of aquatic organisms on MU dynamics, which suggests a different contribution of two MU transmission routes for aquatic hosts (trophic vs environmental transmission) depending on local abiotic factors. DOI: http://dx.doi.org/10.7554/eLife.07616.001
Paul D R Johnson - One of the best experts on this subject based on the ideXlab platform.
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Mycobacterium ulcerans dna in bandicoot excreta in buruli ulcer endemic area northern queensland australia
Emerging Infectious Diseases, 2017Co-Authors: Katharina Roltgen, Gerd Pluschke, Paul D R Johnson, Janet A. M. FyfeAbstract:To identify potential reservoirs/vectors of Mycobacterium ulcerans in northern Queensland, Australia, we analyzed environmental samples collected from the Daintree River catchment area, to which Buruli ulcer is endemic, and adjacent coastal lowlands by species-specific PCR. We detected M. ulcerans DNA in soil, mosquitoes, and excreta of bandicoots, which are small terrestrial marsupials.
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Mycobacterium ulcerans low infectious dose and mechanical transmission support insect bites and puncturing injuries in the spread of Buruli ulcer
PLoS neglected tropical diseases, 2017Co-Authors: John R. Wallace, Jessica L Porter, Kirstie M. Mangas, Renee Marcsisin, Sacha J. Pidot, Brian O. Howden, Till F. Omansen, Weiguang Zeng, Jason K. Axford, Paul D R JohnsonAbstract:Addressing the transmission enigma of the neglected disease Buruli ulcer (BU) is a World Health Organization priority. In Australia, we have observed an association between mosquitoes harboring the causative agent, Mycobacterium ulcerans, and BU. Here we tested a contaminated skin model of BU transmission by dipping the tails from healthy mice in cultures of the causative agent, Mycobacterium ulcerans. Tails were exposed to mosquito (Aedes notoscriptus and Aedes aegypti) blood feeding or punctured with sterile needles. Two of 12 of mice with M. ulcerans contaminated tails exposed to feeding A. notoscriptus mosquitoes developed BU. There were no mice exposed to A. aegypti that developed BU. Eighty-eight percent of mice (21/24) subjected to contaminated tail needle puncture developed BU. Mouse tails coated only in bacteria did not develop disease. A median incubation time of 12 weeks, consistent with data from human infections, was noted. We then specifically tested the M. ulcerans infectious dose-50 (ID50) in this contaminated skin surface infection model with needle puncture and observed an ID50 of 2.6 colony-forming units. We have uncovered a biologically plausible mechanical transmission mode of BU via natural or anthropogenic skin punctures.
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Map showing the distribution of collection sites for possum faeces, indicating the locations of positive samples for Mycobacterium ulcerans DNA by real-time IS2404 PCR.
2014Co-Authors: Connor Carson, Caroline J Lavender, Paul D R Johnson, Kathrine A. Handasyde, Carolyn R. O'brien, Nick Hewitt, Janet A. M. FyfeAbstract:The locations of positive ringtail faecal samples are shown as red ovals; positive brushtail samples are shown as black ovals: negative samples are shown in white. The dotted circle shows a significant non-random clustering of Mycobacterium ulcerans positive possum faecal samples identified by spatial scan statistics (P
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the incubation period of buruli ulcer Mycobacterium ulcerans infection
PLOS Neglected Tropical Diseases, 2013Co-Authors: Jason A Trubiano, Caroline J Lavender, Janet Fyfe, Simone Bittmann, Paul D R JohnsonAbstract:Introduction Buruli Ulcer (BU) is caused by the environmental microbe Mycobacterium ulcerans. Despite unclear transmission, contact with a BU endemic region is the key known risk factor. In Victoria, Australia, where endemic areas have been carefully mapped, we aimed to estimate the Incubation Period (IP) of BU by interviewing patients who reported defined periods of contact with an endemic area prior to BU diagnosis. Method A retrospective review was undertaken of 408 notifications of BU in Victoria from 2002 to 2012. Telephone interviews using a structured questionnaire and review of notification records were performed. Patients with a single visit exposure to a defined endemic area were included and the period from exposure to disease onset determined (IP). Results We identified 111 of 408 notified patients (27%) who had a residential address outside a known endemic area, of whom 23 (6%) reported a single visit exposure within the previous 24 months. The median age of included patients was 30 years (range: 6 to 73) and 65% were male. 61% had visited the Bellarine Peninsula, currently the most active endemic area. The median time from symptom onset to diagnosis was 71 days (range: 34–204 days). The midpoint of the reported IP range was utilized to calculate a point estimate of the IP for each case. Subsequently, the mean IP for the cohort was calculated at 135 days (IQR: 109–160; CI 95%: 113.9–156), corresponding to 4.5 months or 19.2 weeks. The shortest IP recorded was 32 days and longest 264 days (Figure 1 & 2). IP did not vary for variables investigated. Conclusions The estimated mean IP of BU in Victoria is 135 days (IQR: 109–160 days), 4.5 months. The shortest recorded was IP 34 days and longest 264 days. A greater understanding of BU IP will aid clinical risk assessment and future research.
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Mycobacterium ulcerans infection in two alpacas
Australian Veterinary Journal, 2013Co-Authors: Carolyn R Obrien, G Kuseff, E Mcmillan, Christina Mccowan, Caroline J Lavender, Maria Globan, I Jerrett, Frances Oppedisano, Paul D R JohnsonAbstract:Background An ulcerative dermopathy caused by Mycobacterium ulcerans is described in two alpacas (Vicugna pacos) domiciled in endemic areas of Victoria, Australia. Results The diagnosis was confirmed in both cases by PCR targeting the M. ulcerans-specific insertion sequence, IS2404. Extensive wound debridement and bandaging was effective in controlling local disease in one alpaca, although the animal was eventually euthanased because of suspected disease recurrence at other anatomical sites. Treatment was not undertaken in the second animal, but the results of a complete necropsy are described. Investigation of the environs of the second animal yielded low levels of M. ulcerans DNA associated with a variety of samples. The potential use of adjunctive antibiotic therapies directed against M. ulcerans infection in this species is discussed. Conclusion Mycobacterium ulcerans infection should be suspected in alpacas domiciled in endemic areas and presented with ulcerative skin disease.
Gerd Pluschke - One of the best experts on this subject based on the ideXlab platform.
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Mycobacterium ulcerans dna in bandicoot excreta in buruli ulcer endemic area northern queensland australia
Emerging Infectious Diseases, 2017Co-Authors: Katharina Roltgen, Gerd Pluschke, Paul D R Johnson, Janet A. M. FyfeAbstract:To identify potential reservoirs/vectors of Mycobacterium ulcerans in northern Queensland, Australia, we analyzed environmental samples collected from the Daintree River catchment area, to which Buruli ulcer is endemic, and adjacent coastal lowlands by species-specific PCR. We detected M. ulcerans DNA in soil, mosquitoes, and excreta of bandicoots, which are small terrestrial marsupials.
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structure activity relationship studies on the macrolide exotoxin mycolactone of Mycobacterium ulcerans
PLOS Neglected Tropical Diseases, 2013Co-Authors: Jean Pierre Dangy, Philipp Gersbach, Claudio Bomio, Karl-heinz Altmann, Nicole Scherr, Gerd Pluschke, Jun LiAbstract:BACKGROUND: Mycolactones are a family of polyketide-derived macrolide exotoxins produced by Mycobacterium ulcerans, the causative agent of the chronic necrotizing skin disease Buruli ulcer. The toxin is synthesized by polyketide synthases encoded by the virulence plasmid pMUM. The apoptotic, necrotic and immunosuppressive properties of mycolactones play a central role in the pathogenesis of M. ulcerans. METHODOLOGYPRINCIPAL FINDINGS: We have synthesized and tested a series of mycolactone derivatives to conduct structure-activity relationship studies. Flow cytometry, fluorescence microscopy and Alamar Blue-based metabolic assays were used to assess activities of mycolactones on the murine L929 fibroblast cell line. Modifications of the C-linked upper side chain (comprising C12-C20) caused less pronounced changes in cytotoxicity than modifications in the lower C5-O-linked polyunsaturated acyl side chain. A derivative with a truncated lower side chain was unique in having strong inhibitory effects on fibroblast metabolism and cell proliferation at non-cytotoxic concentrations. We also tested whether mycolactones have antimicrobial activity and found no activity against representatives of Gram-positive (Streptococcus pneumoniae) or Gram-negative bacteria (Neisseria meningitis and Escherichia coli), the fungus Saccharomyces cerevisae or the amoeba Dictyostelium discoideum. CONCLUSION: Highly defined synthetic compounds allowed to unambiguously compare biological activities of mycolactones expressed by different M. ulcerans lineages and may help identifying target structures and triggering pathways.
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immunosuppression and treatment associated inflammatory response in patients with Mycobacterium ulcerans infection buruli ulcer
Expert Opinion on Biological Therapy, 2009Co-Authors: Daniela Schutte, Gerd PluschkeAbstract:Buruli ulcer is a necrotizing skin disease caused by Mycobacterium ulcerans. Major necrosis with abundant clusters of extracellularly replicating mycobacteria and only minor leukocyte infiltration are characteristic histopathologic features of the disease. Mycolactone, a cytotoxic macrolide exotoxin of M. ulcerans, plays a key role in the development of this pathology. Antimicrobial therapy, such as rifampicin/streptomycin that was recently introduced, seems to lead to phagocytosis of mycobacteria and massive leukocyte infiltration, which culminates in the development of ectopic lymphoid structures in the lesions. Whereas the curative effect of the antibiotic treatment may be supported by immune defense mechanisms, persisting mycobacterial antigens and immunostimulators occasionally also seem to cause apparent reactivation of the disease. This seems to be related to excessive immunostimulation rather than to incomplete killing of the pathogen.
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evaluation of decontamination methods and growth media for primary isolation of Mycobacterium ulcerans from surgical specimens
Journal of Clinical Microbiology, 2004Co-Authors: Dorothy Yeboahmanu, Ernestina Mensahquainoo, Samuel Owusu, David Oforiadjei, Thomas Bodmer, Gerd PluschkeAbstract:We evaluated four decontamination methods and one nondecontamination procedure in combination with four egg-based media for the primary isolation of Mycobacterium ulcerans from tissue specimens. With mycobacterial recovery and contamination rates of 75.6 and 2.4%, respectively, the combination of the oxalic acid decontamination method with Lowenstein-Jensen medium supplemented with glycerol yielded the best results.
