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Trends in Microbiology Nov 2022
Topics: Mycobacterium ulcerans
PubMed: 36163220
DOI: 10.1016/j.tim.2022.08.012 -
The American Journal of Tropical... Apr 2022Whether Mycobacterium ulcerans, the etiological agent of Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely related...
Whether Mycobacterium ulcerans, the etiological agent of Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely related Mycobacterium species, has not been established. Six M. ulcerans strains were exposed to a progressive depletion in oxygen for 2 months, using the Wayne model of dormancy previously described for M. tuberculosis, and further examined by microscopy after staining of dynamic, dormant, and dead mycobacteria (DDD staining), microcalorimetry and subculture in the presence of dead and replicative M. ulcerans as controls. Mycobacterium ulcerans CU001 strain died during the progressive oxygen depletion and four of five remaining strains exhibited Nile red-stained intracellular lipid droplets and a 14- to 20-day regrowth when exposed to ambient air, consistent with dormancy. A fifth M. ulcerans 19423 strain stained negative in DDD staining 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, warrants further investigations in the natural ecological niches where M. ulcerans thrive as well as in Buruli ulcer lesions.
PubMed: 35405654
DOI: 10.4269/ajtmh.21-1327 -
Journal of Clinical Microbiology Mar 2020
PubMed: 32213576
DOI: 10.1128/JCM.02059-18 -
Emerging Infectious Diseases Dec 2020
Topics: Buruli Ulcer; Humans; Mycobacterium ulcerans; Skin Ulcer
PubMed: 33220026
DOI: 10.3201/eid2612.200744 -
Immunological Reviews May 2021Buruli ulcer is an emerging infectious disease associated with high morbidity and unpredictable outbreaks. It is caused by Mycobacterium ulcerans, a slow-growing... (Review)
Review
Buruli ulcer is an emerging infectious disease associated with high morbidity and unpredictable outbreaks. It is caused by Mycobacterium ulcerans, a slow-growing pathogen evolutionarily shaped by the acquisition of a plasmid involved in the production of a potent macrolide-like cytotoxin and by genome rearrangements and downsizing. These events culminated in an uncommon infection pattern, whereby M. ulcerans is both able to induce the initiation of the inflammatory cascade and the cell death of its proponents, as well as to survive within the phagosome and in the extracellular milieu. In such extreme conditions, the host is sentenced to rely on a highly orchestrated genetic landscape to be able to control the infection. We here revisit the dynamics of M. ulcerans infection, drawing parallels from other mycobacterioses and integrating the most recent knowledge on its evolution and pathogenicity in its interaction with the host immune response.
Topics: Buruli Ulcer; Humans; Mycobacterium ulcerans
PubMed: 33682158
DOI: 10.1111/imr.12958 -
Human Genetics Jun 2020Buruli ulcer, the third most common mycobacterial disease worldwide, is caused by Mycobacterium ulcerans and characterized by devastating necrotizing skin lesions.... (Review)
Review
Buruli ulcer, the third most common mycobacterial disease worldwide, is caused by Mycobacterium ulcerans and characterized by devastating necrotizing skin lesions. Susceptibility to Buruli ulcer is thought to depend on host genetics, but very few genetic studies have been performed. The identification of a microdeletion on chromosome 8 in a familial form of severe Buruli ulcer suggested a monogenic basis of susceptibility. The role of common host genetic variants in Buruli ulcer development has been investigated in only three candidate-gene studies targeting genes involved in mycobacterial diseases. A recent genome-wide association study suggested a probable role for long non-coding RNAs and strengthened the contribution of autophagy as a major defense mechanism against mycobacteria. In this review, we summarize the history, epidemiological and clinical aspects of Buruli ulcer, focusing particularly on genetic findings relating to susceptibility to this disease. Finally, we discuss exciting new genetic avenues arising, in particular, from studies of mouse models, and the need for different disciplines to work together, to benefit from the extensive work on other mycobacterial diseases, mostly tuberculosis and leprosy. We are convinced that such pooling of effort will lead to the development of efficient novel strategies for combatting Buruli ulcer.
Topics: Buruli Ulcer; Genetic Predisposition to Disease; Genome-Wide Association Study; Host-Pathogen Interactions; Human Genetics; Humans; Mycobacterium ulcerans
PubMed: 32266523
DOI: 10.1007/s00439-020-02163-1 -
Methods in Molecular Biology (Clifton,... 2022Primary isolation of Mycobacterium ulcerans is the separation and growth of the bacterium from a mixed population either in clinical specimen or environmental specimen...
Primary isolation of Mycobacterium ulcerans is the separation and growth of the bacterium from a mixed population either in clinical specimen or environmental specimen in pure cultures. It is a crucial activity as it can be used to monitor antimicrobial treatment, surveillance for antimicrobial resistance, and molecular epidemiology studies toward understanding pathogen ecology and transmission as well as pathogen biology. The process involves removal of unwanted fast-growing bacteria using 5% oxalic acid, inoculation on Lowenstein-Jensen medium supplemented with glycerol, and incubation at temperatures between 30 °C and 33 °C.
Topics: Anti-Infective Agents; Culture Media; Glycerol; Mycobacterium ulcerans
PubMed: 34643898
DOI: 10.1007/978-1-0716-1779-3_3 -
Frontiers in Immunology 2020
Topics: Animals; Bacterial Vaccines; Glycolipids; Humans; Mycobacterium; Mycobacterium Infections
PubMed: 33133110
DOI: 10.3389/fimmu.2020.603900 -
Expert Review of Clinical Pharmacology Apr 2020Pharmacological treatment of Buruli ulcer ( infection; BU) is highly effective, as shown in two randomized trials in Africa. (Review)
Review
INTRODUCTION
Pharmacological treatment of Buruli ulcer ( infection; BU) is highly effective, as shown in two randomized trials in Africa.
AREAS COVERED
We review BU drug treatment - in vitro, in vivo and clinical trials (PubMed: '(Buruli OR (Mycobacterium AND ulcerans)) AND (treatment OR therapy).' We also highlight the pathogenesis of infection that is dominated by mycolactone, a secreted exotoxin, that causes skin and soft tissue necrosis, and impaired immune response and tissue repair. Healing is slow, due to the delayed wash-out of mycolactone. An array of repurposed tuberculosis and leprosy drugs appears effective in vitro and in animal models. In clinical trials and observational studies, only rifamycins (notably, rifampicin), macrolides (notably, clarithromycin), aminoglycosides (notably, streptomycin) and fluoroquinolones (notably, moxifloxacin, and ciprofloxacin) have been tested.
EXPERT OPINION
A combination of rifampicin and clarithromycin is highly effective but lesions still take a long time to heal. Novel drugs like telacebec have the potential to reduce treatment duration but this drug may remain unaffordable in low-resourced settings. Research should address ulcer treatment in general; essays to measure mycolactone over time hold promise to use as a readout for studies to compare drug treatment schedules for larger lesions of Buruli ulcer.
Topics: Animals; Anti-Bacterial Agents; Buruli Ulcer; Drug Repositioning; Drug Therapy, Combination; Humans; Macrolides; Mycobacterium ulcerans; Randomized Controlled Trials as Topic; Wound Healing
PubMed: 32310683
DOI: 10.1080/17512433.2020.1752663