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The International Journal of Lower... Sep 2015Buruli ulcer (BU) is caused by Mycobacterium ulcerans and can manifest as a simple nodule or as aggressive skin ulcers leading to debilitating osteoarthritis or limb... (Review)
Review
Buruli ulcer (BU) is caused by Mycobacterium ulcerans and can manifest as a simple nodule or as aggressive skin ulcers leading to debilitating osteoarthritis or limb deformity. The disease is more prevalent in those living in remote rural areas, especially in children younger than 15 years. The exact mode of transmission is possibly through traumatic skin lesions contaminated by M ulcerans. IS2404 polymerase chain reaction from ulcer swabs or biopsies is a rapid method for confirmation of BU. In coendemic countries, HIV infection complicates the progression of BU, leading to rapidly spreading osteomyelitis. Treatment is principally medical, with antitubercular drugs, and surgery is utilized for complicated disease. Because of ineffective vaccination, primary prevention is the best option for control of the disease.
Topics: Buruli Ulcer; Disease Management; Global Health; Humans; Incidence; Mycobacterium ulcerans; Neglected Diseases
PubMed: 26286931
DOI: 10.1177/1534734615599653 -
ACS Infectious Diseases Aug 2022The steroid binding CYP142 cytochrome P450 enzymes of species are involved in the metabolism of cholesterol and its derivatives. The equivalent enzyme from was studied...
The steroid binding CYP142 cytochrome P450 enzymes of species are involved in the metabolism of cholesterol and its derivatives. The equivalent enzyme from was studied to compare the degree of functional conservation between members of this CYP family. We compared substrate binding of the CYP142A3 enzymes of and and CYP142A1 from using UV-vis spectroscopy. The catalytic oxidation of cholesterol derivatives by all three enzymes was undertaken. Both CYP142A3 enzymes were structurally characterized by X-ray crystallography. The amino acid sequences of the CYP142A3 enzymes are more similar to CYP142A1 from than CYP142A2 from . Both CYP142A3 enzymes have substrate binding properties, which are more resemblant to CYP142A1 than CYP142A2. The cholest-4-en-3-one-bound X-ray crystal structure of both CYP142A3 enzymes were determined at a resolution of <1.8 Å, revealing the substrate binding mode at a high level of detail. The structures of the cholest-4-en-3-one binding CYP142 enzymes from and demonstrate how the steroid binds in the active site of these enzymes. They provide an explanation for the high selectivity of the enzyme for terminal methyl C-H bond oxidation to form 26-hydroxy derivatives. These enzymes in pathogenic Mycobacterium species are candidates for inhibition. The work here demonstrates that similar drug molecules could target these CYP142 enzymes from different species in order to combat Buruli ulcer or tuberculosis.
Topics: Cholesterol; Cytochrome P-450 Enzyme System; Humans; Mycobacterium marinum; Mycobacterium tuberculosis; Mycobacterium ulcerans; Tuberculosis
PubMed: 35881654
DOI: 10.1021/acsinfecdis.2c00215 -
PLoS Neglected Tropical Diseases Apr 2017Addressing the transmission enigma of the neglected disease Buruli ulcer (BU) is a World Health Organization priority. In Australia, we have observed an association...
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.
Topics: Aedes; Animals; Australia; Buruli Ulcer; Female; Insect Bites and Stings; Mice, Inbred BALB C; Mycobacterium ulcerans; Needlestick Injuries
PubMed: 28410412
DOI: 10.1371/journal.pntd.0005553 -
PLoS Neglected Tropical Diseases Dec 2021Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, an environmental mycobacterium. Although transmission of M. ulcerans remains poorly...
BACKGROUND
Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, an environmental mycobacterium. Although transmission of M. ulcerans remains poorly understood, the main identified risk factor for acquiring Buruli ulcer is living in proximity of potentially contaminated water sources. Knowledge about the clinical features of Buruli ulcer and its physiopathology is increasing, but little is known about recurrence due to reinfection.
METHODOLOGY/PRINCIPAL FINDINGS
We describe two patients with Buruli ulcer recurrence due to reinfection with M. ulcerans, as demonstrated by comparisons of DNA from the strains isolated at the time of the first diagnosis and at recurrence. Based on the spatial distribution of M. ulcerans genotypes in this region and a detailed study of the behavior of these two patients with respect to sources of water as well as water bodies and streams, we formulated hypotheses concerning the sites at which they may have been contaminated.
CONCLUSIONS/SIGNIFICANCE
Second episodes of Buruli ulcer may occur through reinfection, relapse or a paradoxical reaction. We formally demonstrated that the recurrence in these two patients was due to reinfection. Based on the sites at which the patients reported engaging in activities relating to water, we were able to identify possible sites of contamination. Our findings indicate that the non-random distribution of M. ulcerans genotypes in this region may provide useful information about activities at risk.
Topics: Adult; Benin; Buruli Ulcer; Child; DNA, Bacterial; Female; Genotype; Humans; Male; Mycobacterium ulcerans; Phylogeny; Reinfection
PubMed: 34962930
DOI: 10.1371/journal.pntd.0010053 -
The Medical Journal of Australia Jan 2007
Topics: Anti-Bacterial Agents; Australia; Combined Modality Therapy; Environmental Exposure; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Practice Guidelines as Topic; Skin Diseases, Bacterial; Skin Ulcer
PubMed: 17223762
DOI: 10.5694/j.1326-5377.2007.tb00799.x -
Journal of Bacteriology Feb 2013In 2004, a previously undiscovered mycobacterium resembling Mycobacterium ulcerans (the agent of Buruli ulcer) was reported in an outbreak of a lethal mycobacteriosis in...
In 2004, a previously undiscovered mycobacterium resembling Mycobacterium ulcerans (the agent of Buruli ulcer) was reported in an outbreak of a lethal mycobacteriosis in a laboratory colony of the African clawed frog Xenopus tropicalis. This mycobacterium makes mycolactone and is one of several strains of M. ulcerans-like mycolactone-producing mycobacteria recovered from ectotherms around the world. Here, we describe the complete 6,399,543-bp genome of this frog pathogen (previously unofficially named "Mycobacterium liflandii"), and we show that it has undergone an intermediate degree of reductive evolution between the M. ulcerans Agy99 strain and the fish pathogen Mycobacterium marinum M strain. Like M. ulcerans Agy99, it has the pMUM mycolactone plasmid, over 200 chromosomal copies of the insertion sequence IS2404, and a high proportion of pseudogenes. However, M. liflandii has a larger genome that is closer in length, sequence, and architecture to M. marinum M than to M. ulcerans Agy99, suggesting that the M. ulcerans Agy99 strain has undergone accelerated evolution. Scrutiny of the genes specifically lost suggests that M. liflandii is a tryptophan, tyrosine, and phenylalanine auxotroph. A once-extensive M. marinum-like secondary metabolome has also been diminished through reductive evolution. Our analysis shows that M. liflandii, like M. ulcerans Agy99, has the characteristics of a niche-adapted mycobacterium but also has several distinctive features in important metabolic pathways that suggest that it is responding to different environmental pressures, supporting earlier proposals that it could be considered an M. ulcerans ecotype, hence the name M. ulcerans ecovar Liflandii.
Topics: Animals; Anti-Bacterial Agents; Chromosome Mapping; Chromosomes, Bacterial; Drug Resistance, Bacterial; Genome, Bacterial; Multigene Family; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Ranidae
PubMed: 23204453
DOI: 10.1128/JB.02132-12 -
Toxins Mar 2019Buruli ulcer is a neglected tropical infectious disease, produced by the environmentally persistent pathogen (MU). Neither the ecological niche nor the exact mode of...
Buruli ulcer is a neglected tropical infectious disease, produced by the environmentally persistent pathogen (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.
Topics: Bacteriological Techniques; Environment; High-Throughput Nucleotide Sequencing; Macrolides; Mycobacterium ulcerans; Transcriptome
PubMed: 30836720
DOI: 10.3390/toxins11030146 -
Expert Review of Molecular Diagnostics 2024
Topics: Humans; Buruli Ulcer; Mycobacterium ulcerans; Macrolides
PubMed: 38073533
DOI: 10.1080/14737159.2023.2294333 -
Methods in Molecular Biology (Clifton,... 2022Mycobacterium ulcerans is a slow-growing environmental bacterium that causes a severe skin disease known as Buruli ulcer. Identification of environmental reservoirs and...
Mycobacterium ulcerans is a slow-growing environmental bacterium that causes a severe skin disease known as Buruli ulcer. Identification of environmental reservoirs and agents associated with disease transmission is crucial to understanding the risk factors for this emerging infectious disease. Since culture of M. ulcerans from the environment still proves to be problematic, the direct detection of M. ulcerans in environmental samples via PCR has become increasingly important as the research community seeks to elucidate the mode(s) of transmission and environmental reservoir(s) of this elusive organism.
Topics: Buruli Ulcer; DNA Transposable Elements; DNA, Bacterial; Humans; Mycobacterium ulcerans; Real-Time Polymerase Chain Reaction
PubMed: 34643902
DOI: 10.1007/978-1-0716-1779-3_7 -
PloS One 2016Ivory Coast is a West African country with the highest reported cases of Buruli ulcer, a disabling subcutaneous infection due to Mycobacterium ulcerans. However, the...
BACKGROUND
Ivory Coast is a West African country with the highest reported cases of Buruli ulcer, a disabling subcutaneous infection due to Mycobacterium ulcerans. However, the prevalence of environmental M. ulcerans is poorly known in this country.
METHODS
We collected 496 environmental specimens consisting of soil (n = 100), stagnant water (n = 200), plants (n = 100) and animal feces (n = 96) in Ivory Coast over five months in the dry and wet seasons in regions which are free of Buruli ulcer (control group A; 250 specimens) and in regions where the Buruli ulcer is endemic (group B; 246 specimens). After appropriate total DNA extraction incorporating an internal control, the M. ulcerans IS2404 and KR-B gene were amplified by real-time PCR in samples. In parallel, a calibration curve was done for M. ulcerans Agy99 IS2404 and KR-B gene.
RESULTS
Of 460 samples free of PCR inhibition, a positive real-time PCR detection of insertion sequence IS2404 and KR-B gene was observed in 1/230 specimens in control group A versus 9/230 specimens in group B (P = 0.02; Fisher exact test). Positive specimens comprised seven stagnant water specimens, two feces specimens confirmed to be of Thryonomys swinderianus (agouti) origin by real-time PCR of the cytb gene; and one soil specimen. Extrapolation from the calibration curves indicated low inoculums ranging from 1 to 102 mycobacteria/mL.
CONCLUSION
This study confirms the presence of M. ulcerans in the watery environment surrounding patients with Buruli ulcer in Ivory Coast. It suggests that the agouti, which is in close contacts with populations, could play a role in the environmental cycle of M. ulcerans, as previously suggested for the closely related possums in Australia.
Topics: Animals; Cote d'Ivoire; DNA, Bacterial; Feces; Mycobacterium ulcerans; Real-Time Polymerase Chain Reaction; Soil Microbiology
PubMed: 26982581
DOI: 10.1371/journal.pone.0151567