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Trends in Microbiology Nov 2022
Topics: Mycobacterium ulcerans
PubMed: 36163220
DOI: 10.1016/j.tim.2022.08.012 -
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 -
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 -
Bulletin of the World Health... Oct 2005Mycobacterium ulcerans disease (Buruli ulcer) is an important health problem in several west African countries. It is prevalent in scattered foci around the world,... (Review)
Review
Mycobacterium ulcerans disease (Buruli ulcer) is an important health problem in several west African countries. It is prevalent in scattered foci around the world, predominantly in riverine areas with a humid, hot climate. We review the epidemiology, bacteriology, transmission, immunology, pathology, diagnosis and treatment of infections. M. ulcerans is an ubiquitous micro-organism and is harboured by fish, snails, and water insects. The mode of transmission is unknown. Lesions are most common on exposed parts of the body, particularly on the limbs. Spontaneous healing may occur. Many patients in endemic areas present late with advanced, severe lesions. BCG vaccination yields a limited, relatively short-lived, immune protection. Recommended treatment consists of surgical debridement, followed by skin grafting if necessary. Many patients have functional limitations after healing. Better understanding of disease transmission and pathogenesis is needed for improved control and prevention of Buruli ulcer.
Topics: Africa, Western; Humans; Meta-Analysis as Topic; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans
PubMed: 16283056
DOI: No ID Found -
Scientific Reports Feb 2019The opportunistic pathogen Mycobacterium ulcerans, which is responsible for Buruli ulcer, synthesizes a series of plasmid-encoded macrolide exotoxins termed...
The opportunistic pathogen Mycobacterium ulcerans, which is responsible for Buruli ulcer, synthesizes a series of plasmid-encoded macrolide exotoxins termed mycolactones. These toxins destabilize cell membranes and induce apoptosis-associated pleiotropic effects including tissue destruction, analgesic and anti-inflammatory effects. Despite its medical interest, M. ulcerans is primarily an environmental mycobacterium and the primary functions of mycolactones in the natural ecosystems are unknown. High throughput biochemical profiling findings suggested that M. ulcerans may interact with fungi. Here, we report that semi-purified and purified mycolactones significantly enhance spore germination of Scedosporium apiospermum, Fusarium equiseti and Mucor circinelloides; and that M. ulcerans mycolactones significantly attract colonies of M. circinelloides whereas no significant effect was observed on S. apiospermum and F. equiseti. These experimental results suggest that mycolactones exhibit a chemoattractant activity independent of their cytotoxicity. In natural ecosystems, M. ulcerans mycolactones may act as spore germination inducers and chemoattractants for some fungi, suggesting a novel role for this unique class of mycobacterial toxins in natural ecosystems.
Topics: Apoptosis; Ecosystem; Exotoxins; Fungi; Humans; Macrolides; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans
PubMed: 30816261
DOI: 10.1038/s41598-019-39927-3 -
Journal of Medical Microbiology Jun 1999
Review
Topics: Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Skin Ulcer
PubMed: 10359298
DOI: 10.1099/00222615-48-6-511 -
Immunological Reviews May 2021Mycobacterium ulcerans causes Buruli ulcer, a neglected tropical skin disease manifesting as chronic wounds that can leave victims with major, life-long deformity and... (Review)
Review
Mycobacterium ulcerans causes Buruli ulcer, a neglected tropical skin disease manifesting as chronic wounds that can leave victims with major, life-long deformity and disability. Differently from other mycobacterial pathogens, M ulcerans produces mycolactone, a diffusible lipid factor with unique cytotoxic and immunomodulatory properties. Both traits result from mycolactone targeting Sec61, the entry point of the secretory pathway in eukaryotic cells. By inhibiting Sec61, mycolactone prevents the host cell's production of secreted proteins, and most of its transmembrane proteins. This molecular blockade dramatically alters the functions of immune cells, thereby the generation of protective immunity. Moreover, sustained inhibition of Sec61 triggers proteotoxic stress responses leading to apoptotic cell death, which can stimulate vigorous immune responses. The dynamics of bacterial production of mycolactone and elimination by infected hosts thus critically determine the balance between its immunostimulatory and immunosuppressive effects. Following an introduction summarizing the essential information on Buruli ulcer disease, this review focuses on the current state of knowledge regarding mycolactone's regulation and biodistribution. We then detail the consequences of mycolactone-mediated Sec61 blockade on initiation and maintenance of innate and adaptive immune responses. Finally, we discuss the key questions to address in order to improve immunity to M ulcerans, and how increased knowledge of mycolactone biology may pave the way to innovative therapeutics.
Topics: Buruli Ulcer; Humans; Macrolides; Mycobacterium ulcerans; Tissue Distribution
PubMed: 33607704
DOI: 10.1111/imr.12956 -
Methods in Molecular Biology (Clifton,... 2022Enhanced international research efforts since the establishment of the Global BU Initiative in 1998 by the WHO have helped to advance our understanding of the...
Enhanced international research efforts since the establishment of the Global BU Initiative in 1998 by the WHO have helped to advance our understanding of the epidemiology, and pathogenesis of Mycobacterium ulcerans infections. Improved methods to cultivate the extremely slow-growing pathogen from BU lesions have laid the groundwork for a variety of studies using M. ulcerans isolates, including the analysis of the genome and proteome of the pathogen, as well as drug susceptibility testing and analyses of host-pathogen interactions in vitro and in animal models. The identification of specific, high-copy number target sequences in the genome of M. ulcerans has enabled the development of diagnostic tests and assays to detect the pathogen in the environment. Important research questions remain about the reservoir(s) of M. ulcerans in aquatic environments, factors leading to or promoting transmission to hosts, and host-pathogen interactions resulting in chronic infection versus spontaneous healing.
Topics: Animals; Buruli Ulcer; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycobacterium ulcerans; Persistent Infection
PubMed: 34643896
DOI: 10.1007/978-1-0716-1779-3_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 -
Revue Scientifique Et Technique... Apr 2001Mycobacterium ulcerans infection, or Buruli ulcer, is the third most frequent mycobacterial disease in humans, often causing serious deformities and disability. The... (Review)
Review
Mycobacterium ulcerans infection, or Buruli ulcer, is the third most frequent mycobacterial disease in humans, often causing serious deformities and disability. The disease is most closely associated with tropical wetlands, especially in west and central Africa. Most investigators believe that the aetiological agent proliferates in mud beneath stagnant waters. Modes of transmission may involve direct contact with the contaminated environment, aerosols from water surfaces, and water-dwelling fauna (e.g. insects). Person-to-person transmission is rare. Trauma at the site of skin contamination by M. ulcerans appears to play an important role in initiating disease. Once introduced into the skin or subcutaneous tissue, M. ulcerans multiplies and produces a toxin that causes necrosis. However, the type of disease induced varies from a localised nodule or ulcer, to widespread ulcerative or non-ulcerative disease and osteomyelitis. Although culture of M. ulcerans from a patient was first reported in 1948, attempts to culture the mycobacterium from many specimens of flora and fauna have been unsuccessful. Failure to cultivate this organism from nature may be attributable to inadequate sampling, conditions of transport, decontamination and culture of this fastidious heat-sensitive organism, and to a long generation time relative to that of other environmental mycobacteria. Nevertheless, recent molecular studies using specific primers have revealed M. ulcerans in water, mud, fish and insects. Although no natural reservoir has been found, the possibility that M. ulcerans may colonise microfauna such as free-living amoebae has not been investigated. The host range of experimental infection by M. ulcerans includes lizards, amphibians, chick embryos, possums, armadillos, rats, mice and cattle. Natural infections have been observed only in Australia, in koalas, ringtail possums and a captive alpaca. The lesions were clinically identical to those observed in humans. Mycobacterium ulcerans infection is a rapidly re-emerging disease in some developing tropical countries. The re-emergence may be related to environmental and socioeconomic factors, for example, deforestation leading to increased flooding, and population expansion without improved agricultural techniques, thus putting more people at risk. Eradication of diseases related to these factors is difficult. Whether wild animals have a role in transmission is an important question that, to date, has been virtually unexplored. To address this question, surveys of wild animals are urgently required in those areas in which Buruli ulcer is endemic.
Topics: Africa; Animals; Animals, Wild; Disease Reservoirs; Humans; Invertebrates; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Water Microbiology
PubMed: 11288515
DOI: 10.20506/rst.20.1.1270