Overview: Mycobacterium ulcerans Disease (Buruli Ulcer)

2021 ◽  
pp. 3-6
Author(s):  
Katharina Röltgen ◽  
Gerd Pluschke
Keyword(s):  
Buruli Ulcer ◽  
Mycobacterium Ulcerans

Interactions between ecological and socio-economic drivers of Buruli ulcer burden in Sub-Saharan Africa: opportunities for an improved control

2018 ◽  
Author(s):  
Andes Garchitorena ◽  
Matthew H. Bonds ◽  
Jean-Francois Guégan ◽  
Benjamin Roche
Keyword(s):  
Socioeconomic Factors ◽  
Disease Transmission ◽  
Access To Health Care ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Sub Saharan Africa ◽  
Aquatic Environments ◽  
Human Populations ◽  
Complex Interactions ◽  
Sub Saharan

This chapter provides an overview of the complex interactions between ecological and socioeconomic factors for the development and control of Buruli ulcer in Sub-Saharan Africa. We review key ecological and evolutionary processes driving the environmental persistence and proliferation of Mycobacterium ulcerans, the causative agent, within aquatic environments, as well as transmission processes from these aquatic environments to human populations. We also outline key socioeconomic factors driving the economic and health burden of Buruli ulcer in endemic regions, revealed by reciprocal feedbacks between poverty, disease transmission from exposure aquatic environments and disease progression to severe stages owing to low access to health care. The implications of such insights for disease control, both in terms of limitations of current strategies and directions for the future, are discussed.

scholarly journals Cellular Immunity Confers Transient Protection in Experimental Buruli Ulcer following BCG or Mycolactone-Negative Mycobacterium ulcerans Vaccination

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e33406 ◽  
Author(s):  
Alexandra G. Fraga ◽  
Teresa G. Martins ◽  
Egídio Torrado ◽  
Kris Huygen ◽  
Françoise Portaels ◽  
...  
Keyword(s):  
Cellular Immunity ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans

scholarly journals Community-based geographical distribution of Mycobacterium ulcerans VNTR-genotypes from the environment and humans in the Nyong valley, Cameroon

2021 ◽  
Vol 49 (1) ◽  
Author(s):  
Francis Zeukeng ◽  
Anthony Ablordey ◽  
Solange E. Kakou-Ngazoa ◽  
Stephen Mbigha Ghogomu ◽  
David N’golo Coulibaly ◽  
...  
Keyword(s):  
Environmental Samples ◽  
Tandem Repeats ◽  
Buruli Ulcer ◽  
Variable Number ◽  
Mycobacterium Ulcerans ◽  
Community Based ◽  
Human Samples ◽  
Route Of Transmission ◽  
Mode Of Transmission ◽  
Animal Reservoirs

Abstract Background Genotyping is a powerful tool for investigating outbreaks of infectious diseases and it can provide useful information such as identifying the source and route of transmission, and circulating strains involved in the outbreak. Genotyping techniques based on variable number of tandem repeats (VNTR) are instrumental in detecting heterogeneity in Mycobacterium ulcerans (MU) and also for discriminating MU from other mycobacteria species. Here, we describe and map the distribution of MU genotypes in Buruli ulcer (BU) endemic communities of the Nyong valley in Cameroon. We also tested the hypothesis of whether the suspected animal reservoirs of BU that share the human microhabitat are shedding contaminated fecal matters and saliva into their surrounding environments. Methods Environmental samples from suspected MU-risk factors and lesion swabs from human patients were sampled in BU-endemic communities and tested for the presence of MU by qPCR targeting three independent sequences (IS2404, IS2606, KR-B). Positive samples to MU were further genotyped by VNTR with confirmation by sequencing of four loci (MIRU1, Locus 6, ST1, Locus 19). Results MU was detected in environmental samples including water bodies (23%), biofilms (14%), detritus (10%), and in human patients (73%). MU genotypes D, W, and C were found both in environmental and human samples. The micro geo-distribution of MU genotypes from communities showed that genotype D is found both in environmental and human samples, while genotypes W and C are specific to environmental samples and human lesions, respectively. No obvious focal grouping of MU genotypes was observed at the community scale. An additional survey in the human microhabitat suggests that domestic and wild animals do not shed MU in their saliva and feces in sampled communities. Conclusions VNTR typing uncovered different MU genotypes circulating in the endemic communities of the Akonolinga district. A MU environmental genotype was found in patients, yet the mechanism of contamination remains to be investigated; and recovering MU in culture from the environment remains key priority to enable a better understanding of the mode of transmission of BU. We also conclude that excretions from suspected animals are unlikely to be major sources of MU in the Nyong Valley in Cameroon.

scholarly journals High-Dose Rifamycins Enable Shorter Oral Treatment in a Murine Model ofMycobacterium ulceransDisease

2018 ◽  
Vol 63 (2) ◽  
pp. e01478-18 ◽  
Author(s):  
Till F. Omansen ◽  
Deepak Almeida ◽  
Paul J. Converse ◽  
Si-Yang Li ◽  
Jin Lee ◽  
...  
Keyword(s):  
Oral Treatment ◽  
Buruli Ulcer ◽  
Indirect Costs ◽  
Ceiling Effect ◽  
Mycobacterium Ulcerans ◽  
High Dose ◽  
Current Standard ◽  
Standard Regimen ◽  
Content Type ◽  
Dose Dependent

ABSTRACTBuruli ulcer (BU), caused byMycobacterium ulcerans, is a neglected tropical skin and soft tissue infection that is associated with disability and social stigma. The mainstay of BU treatment is an 8-week course of rifampin (RIF) at 10 mg/kg of body weight and 150 mg/kg streptomycin (STR). Recently, the injectable STR has been shown to be replaceable with oral clarithromycin (CLR) for smaller lesions for the last 4 weeks of treatment. A shorter, all-oral, highly efficient regimen for BU is needed, as the long treatment duration and indirect costs currently burden patients and health systems. Increasing the dose of RIF or replacing it with the more potent rifamycin drug rifapentine (RPT) could provide such a regimen. Here, we performed a dose-ranging experiment of RIF and RPT in combination with CLR over 4 weeks of treatment in a mouse model ofM. ulceransdisease. A clear dose-dependent effect of RIF on both clinical and microbiological outcomes was found, with no ceiling effect observed with tested doses up to 40 mg/kg. RPT-containing regimens were more effective onM. ulcerans. All RPT-containing regimens achieved culture negativity after only 4 weeks, while only the regimen with the highest RIF dose (40 mg/kg) did so. We conclude that there is dose-dependent efficacy of both RIF and RPT and that a ceiling effect is not reached with the current standard regimen used in the clinic. A regimen based on higher rifamycin doses than are currently being evaluated against tuberculosis in clinical trials could shorten and improve therapy of Buruli ulcer.

scholarly journals Heterogeneity of Mycolactones Produced by Clinical Isolates of Mycobacterium ulcerans: Implications for Virulence

2003 ◽  
Vol 71 (2) ◽  
pp. 774-783 ◽  
Author(s):  
Armand Mve-Obiang ◽  
Richard E. Lee ◽  
Françoise Portaels ◽  
P. L. C. Small
Keyword(s):  
Clinical Evidence ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Tissue Destruction ◽  
The Core ◽  
A Minor ◽  
Layer Chromatography

ABSTRACT Mycobacterium ulcerans is the causative agent of Buruli ulcer, a severe necrotizing skin disease endemic in tropical countries. Clinical evidence suggests that M. ulcerans isolates from Asia, Mexico, and Australia may be less virulent than isolates from Africa. In vivo studies suggest that mycolactone, a polyketide-derived macrolide toxin, plays a major role in the tissue destruction and immune suppression which occur in cases of Buruli ulcer. Mycolactones were extracted from 34 isolates of M. ulcerans representing strains from Africa, Malaysia, Asia, Australia, and Mexico. Thin-layer chromatography, mass spectroscopic analysis, and cytopathic assays of partially purified mycolactones from these isolates revealed that M. ulcerans produces a heterogeneous mixture of mycolactone variants. Mycolactone A/B, the most biologically active mycolactone species, was identified by mass spectroscopy as [M+Na]+ at m/z 765.5 in all cytotoxic isolates except for those from Mexico. Mycolactone C [M+Na]+ at m/z 726.3 was the dominant mycolactone species in eight Australian isolates, and mycolactone D [M+Na]+ m/z 781.2 was characteristic of two Asian strains. Mycolactone species are conserved within specific geographic areas, suggesting that there may be a correlation between mycolactone profile and virulence. In addition, the core lactone, [M+Na]+ m/z 447.4, was identified as a minor species, supporting the hypothesis that mycolactones are synthesized by two polyketide synthases. A cytopathic assay of the core lactone showed that this molecule is sufficient for cytotoxicity, although it is much less potent than the complete mycolactone.

scholarly journals Triple oral beta-lactam containing therapy for Buruli ulcer treatment shortening

2018 ◽  
Author(s):  
María Pilar Arenaz Callao ◽  
Rubén González del Río ◽  
Ainhoa Lucía Quintana ◽  
Charles J. Thompson ◽  
Alfonso Mendoza-Losana ◽  
...  
Keyword(s):  
Inhibitory Concentration ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Amoxicillin Clavulanate ◽  
Low Toxicity ◽  
Potential Use ◽  
Ulcer Treatment

ABSTRACTThe potential use of clinically approved beta-lactams for Buruli ulcer (BU) treatment was investigated with representative classes analyzed in vitro for activity against Mycobacterium ulcerans. Beta-lactams tested were effective alone and displayed a strong synergistic profile in combination with antibiotics currently used to treat BU, i.e. rifampicin and clarithromycin; this activity was further potentiated in the presence of the beta-lactamase inhibitor clavulanate. In addition, quadruple combinations of rifampicin, clarithromycin, clavulanate and beta-lactams resulted in multiplicative reductions in their minimal inhibitory concentration (MIC) values. The MIC of amoxicillin against a panel of clinical isolates decreased more than 200-fold within this quadruple combination. Amoxicillin/clavulanate formulations are readily available with clinical pedigree, low toxicity, and orally and pediatric available; thus, supporting its potential inclusion as a new anti-BU drug in current combination therapies.

scholarly journals Molecular Mechanisms Underpinning the Circulation and Cellular Uptake of Mycobacterium ulcerans Toxin Mycolactone

2021 ◽  
Vol 12 ◽  
Author(s):  
Bruno Tello Rubio ◽  
Florence Bugault ◽  
Blandine Baudon ◽  
Bertrand Raynal ◽  
Sébastien Brûlé ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Molecular Mechanisms ◽  
Scavenger Receptor ◽  
Buruli Ulcer ◽  
Systemic Circulation ◽  
Mycobacterium Ulcerans ◽  
Host Cells ◽  
Ulcer Disease ◽  
Major Mechanism ◽  
Specific Association

Mycolactone is a diffusible lipid toxin produced by Mycobacterium ulcerans, the causative agent of Buruli ulcer disease. Altough bacterially derived mycolactone has been shown to traffic from cutaneous foci of infection to the bloodstream, the mechanisms underpinning its access to systemic circulation and import by host cells remain largely unknown. Using biophysical and cell-based approaches, we demonstrate that mycolactone specific association to serum albumin and lipoproteins is necessary for its solubilization and is a major mechanism to regulate its bioavailability. We also demonstrate that Scavenger Receptor (SR)-B1 contributes to the cellular uptake of mycolactone. Overall, we suggest a new mechanism of transport and cell entry, challenging the dogma that the toxin enters host cells via passive diffusion.

scholarly journals Experimental pieces of evidence for Mycobacterium ulcerans dormancy

2020 ◽  
Author(s):  
A. Loukil ◽  
R. Lalaoui ◽  
H. Bogreau ◽  
S. Regoui ◽  
M. Drancourt ◽  
...  
Keyword(s):  
Physiological State ◽  
Nile Red ◽  
Buruli Ulcer ◽  
Ambient Air ◽  
Opportunistic Pathogen ◽  
Oxygen Depletion ◽  
Mycobacterium Ulcerans ◽  
Ecological Niches ◽  
Intracellular Lipid ◽  
First Time

ABSTRACTBackgroundWhether Mycobacterium ulcerans, the etiological agent of the neglected Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely related Mycobacterium species, is not established.MethodologySix M. ulcerans strains were exposed to a progressive depletion in oxygen for two months, using a previously described Wayne model of dormancy; and further examined by microscopy using DDD staining, microcalorimetry and subculture in the presence of dead and replicative M. ulcerans as controls.Principal Findings/ConclusionsM. ulcerans CU001 strain died during the progressive oxygen depletion and four of five remaining strains exhibited Nile Red-stained intracellular lipid droplets after DDD staining and a 14-20-day regrowth when exposed to ambient air, diagnosing dormancy. A fifth M. ulcerans 19423 strain stained negative in DDD and slowly regrew in 27 days. Three tested M. ulcerans strains yielded microcalorimetric pattern similar to that of the negative (dead) homologous controls, differing from that of the homologous positive (replicative) controls. The relevance of these experimental observations, suggesting a previously unreported dormancy state of M. ulcerans, needs to be investigated in the natural ecological niches where M. ulcerans thrive and in Buruli ulcer lesions.Author summaryMycobacterium ulcerans is an environmental opportunistic pathogen of mammals and humans, causing a subcutaneous necrotizing infection named Buruli ulcer. Molecular detection of M. ulcerans DNA revealed different ecological niches where M. ulcerans may thrive, but the molecular biology approach does not catch the physiological state of M. ulcerans in these different ecological niches. Thus, the reservoir and the mode of transmission of M. ulcerans remain elusive. Here, we investigated experimental dormancy of M. ulcerans by using a previously described Wayne model of dormancy coupled with microscopy using DDD staining, microcalorimetry and subculture. Our findings demonstrate for the first time that some M. ulcerans strains exhibit a physiological state of dormancy; potentially limiting isolation and culture of M. ulcerans from environmental niches.

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