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PloS One 2020Mycobacterium ulcerans is a non-tuberculous environmental mycobacterium responsible for extensive cutaneous and subcutaneous ulcers in mammals, known as Buruli ulcer in...
Mycobacterium ulcerans is a non-tuberculous environmental mycobacterium responsible for extensive cutaneous and subcutaneous ulcers in mammals, known as Buruli ulcer in humans. M. ulcerans has seldom been detected in the faeces of mammals and has not been detected in human faeces. Nevertheless, the detection and isolation of M. ulcerans in animal faeces does not fit with the current epidemiological schemes for the disease. Here, using an experimental model in which rats were fed with 109 colony-forming units of M. ulcerans, we detected M. ulcerans DNA in the faeces of challenged rats for two weeks and along their digestive tract for 10 days. M. ulcerans DNA was further detected in the lymphatic system including in the cervical and axillary lymph nodes and the spleen, but not in any other tissue including healthy and broken skin, 10 days post-challenge. These observations indicate that in some herbivorous mammals, M. ulcerans contamination by the digestive route may precede translocation and limited contamination of the lymphatic tissues without systemic infection. These herbivorous mammals may be sources of M. ulcerans for exposed populations but are unlikely to be reservoirs for the pathogen.
Topics: Animals; DNA, Bacterial; Feces; Gastrointestinal Tract; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Rats; Rats, Long-Evans
PubMed: 33378325
DOI: 10.1371/journal.pone.0230544 -
PLoS Neglected Tropical Diseases Aug 2021Mycobacterium ulcerans is the causative agent of Buruli ulcer, a rare but chronic debilitating skin and soft tissue disease found predominantly in West Africa and... (Review)
Review
Mycobacterium ulcerans is the causative agent of Buruli ulcer, a rare but chronic debilitating skin and soft tissue disease found predominantly in West Africa and Southeast Australia. While a moderate body of research has examined the distribution of M. ulcerans, the specific route(s) of transmission of this bacterium remain unknown, hindering control efforts. M. ulcerans is considered an environmental pathogen given it is associated with lentic ecosystems and human-to-human spread is negligible. However, the pathogen is also carried by various mammals and invertebrates, which may serve as key reservoirs and mechanical vectors, respectively. Here, we examine and review recent evidence from these endemic regions on potential transmission pathways, noting differences in findings between Africa and Australia, and summarising the risk and protective factors associated with Buruli ulcer transmission. We also discuss evidence suggesting that environmental disturbance and human population changes precede outbreaks. We note five key research priorities, including adoption of One Health frameworks, to resolve transmission pathways and inform control strategies to reduce the spread of Buruli ulcer.
Topics: Animals; Buruli Ulcer; Communicable Disease Control; Ecosystem; Environment; Humans; Mycobacterium ulcerans; One Health
PubMed: 34437549
DOI: 10.1371/journal.pntd.0009678 -
Methods in Molecular Biology (Clifton,... 2022Mycobacterium ulcerans is a slow-growing environmental bacterium that causes a severe skin disease known as Buruli ulcer. Rapid detection of M. ulcerans in clinical...
Mycobacterium ulcerans is a slow-growing environmental bacterium that causes a severe skin disease known as Buruli ulcer. Rapid detection of M. ulcerans in clinical specimens is essential for ensuring early diagnosis and prevention of disability. This chapter describes a real-time PCR method for the direct detection of M. ulcerans from a variety of clinical and environmental samples (Fig. 1). Methods for the extraction of DNA from swabs, fresh tissue biopsies, and fixed tissue sections, which are the most common types of specimens used in the diagnosis of Buruli ulcer, are described in Chapter 6 . Chapter 7 describes the appropriate DNA extraction methods for environmental samples including soil, detritus, water, animal feces, and insects, as reliable detection of M. ulcerans in the environment is becoming increasingly important for understanding the ecology and transmission of this elusive pathogen.
Topics: Animals; Buruli Ulcer; DNA Transposable Elements; DNA, Bacterial; Mycobacterium ulcerans; Real-Time Polymerase Chain Reaction
PubMed: 34643903
DOI: 10.1007/978-1-0716-1779-3_8 -
Microbiology Spectrum Jun 2023Mycobacterium ulcerans, an environmental opportunistic pathogen, causes necrotic cutaneous and subcutaneous lesions, named Buruli ulcers, in tropical countries....
Mycobacterium ulcerans, an environmental opportunistic pathogen, causes necrotic cutaneous and subcutaneous lesions, named Buruli ulcers, in tropical countries. PCR-derived tests used to detect M. ulcerans in environmental and clinical samples do not allow one-shot detection, identification, and typing of M. ulcerans among closely related Mycobacterium marinum complex mycobacteria. We established a 385-member M. marinum/M. ulcerans complex whole-genome sequence database by assembling and annotating 341 M. marinum/M. ulcerans complex genomes and added 44 M. marinum/M. ulcerans complex whole-genome sequences already deposited in the NCBI database. Pangenome, core genome, and single-nucleotide polymorphism (SNP) distance-based comparisons sorted the 385 strains into 10 M. ulcerans taxa and 13 M. marinum taxa, correlating with the geographic origin of strains. Aligning conserved genes identified one (proline-proline-glutamate) gene sequence to be species and intraspecies specific, thereby genotyping the 23 M. marinum/M. ulcerans complex taxa. PCR sequencing of the gene correctly genotyped nine M. marinum/M. ulcerans complex isolates among one M. marinum taxon and three M. ulcerans taxa in the African taxon (T2.4). Further, successful gene PCR sequencing in 15/21 (71.4%) swabs collected from suspected Buruli ulcer lesions in Côte d'Ivoire exhibited positive M. ulcerans 2404 real-time PCR and identified the M. ulcerans T2.4.1 genotype in eight swabs and M. ulcerans T2.4.1/T2.4.2 mixed genotypes in seven swabs. gene sequencing could be used as a proxy for whole-genome sequencing for the one-shot detection, identification, and typing of clinical M. ulcerans strains, offering an unprecedented tool for identifying M. ulcerans mixed infections. We describe a new targeted sequencing approach that characterizes the gene to disclose the simultaneous presence of different variants of a single pathogenic microorganism. This approach has direct implications on the understanding of pathogen diversity and natural history and potential therapeutic implications when dealing with obligate and opportunistic pathogens, such as Mycobacterium ulcerans presented here as a prototype.
Topics: Humans; Buruli Ulcer; Mycobacterium ulcerans; Cote d'Ivoire; Real-Time Polymerase Chain Reaction; Personal Protective Equipment
PubMed: 37222600
DOI: 10.1128/spectrum.00342-23 -
Infection, Genetics and Evolution :... Apr 2012Mycobacterium ulcerans (M. ulcerans) causes a devastating infection of the skin and underlying tissue commonly known as Buruli ulcer (BU). Genetic analyses indicate that... (Review)
Review
Mycobacterium ulcerans (M. ulcerans) causes a devastating infection of the skin and underlying tissue commonly known as Buruli ulcer (BU). Genetic analyses indicate that M. ulcerans has a common ancestor with Mycobacterium marinum (M. marinum) and has diverged from this fish and human pathogen perhaps around a million years ago. M. ulcerans is characterized by minimal genetic diversity and since it has a highly clonal population structure, genetic differences between individual isolates reflect changes that have occurred sequentially from their respective progenitors. This feature, which is shared by other bacterial pathogens with low sequence diversity, such as Yersinia pestis and Bordetella pertussis renders M. ulcerans a promising model to reveal evolutionary mechanisms. Until today transmission pathways and environmental reservoirs of M. ulcerans are not entirely explored. However, comparative genome analysis of closely related M. ulcerans isolates is anticipated to give deeper insights into the population structure of this enigmatic mycobacterium.
Topics: Animals; Buruli Ulcer; Chromosomes, Bacterial; DNA Transposable Elements; Evolution, Molecular; Genetic Variation; Genome, Bacterial; Humans; Macrolides; Mycobacterium marinum; Mycobacterium ulcerans; Phylogeny; Plasmids; Virulence Factors
PubMed: 22306192
DOI: 10.1016/j.meegid.2012.01.018 -
PLoS Neglected Tropical Diseases Dec 2023Chronic tropical cutaneous ulcers remain a neglected medical condition in West Africa, particularly Buruli ulcer, which is caused by mycolactone cytotoxin-secreting...
BACKGROUND
Chronic tropical cutaneous ulcers remain a neglected medical condition in West Africa, particularly Buruli ulcer, which is caused by mycolactone cytotoxin-secreting Mycobacterium ulcerans (M. ulcerans). Medical management of this highly debilitating and necrotising skin infection may be modified by colonisation and co-infection of the ulcer by opportunistic and pathogenic microorganisms, which considerably delays and increases the cost of treatment.
METHODOLOGY/PRINCIPAL FINDING
We diagnosed chronic tropical cutaneous ulcers in nine patients in Côte d'Ivoire using M. ulcerans-specific PCRs and culturomics. This revealed M. ulcerans in 7/9 ulcer swabs and 5/9 control swabs as well as an additional 122 bacterial species, 32 of which were specific to ulcers, 61 specifics to the controls, and 29 which were shared, adding 40 bacterial species to those previously reported. Whole genome sequencing of four Bordetella trematum (B. trematum) isolates in four Buruli ulcer swabs and no controls indicated cytolethal distending toxins, as confirmed by cytotoxic assay.
CONCLUSIONS/SIGNIFICANCE
In four cases of Buruli ulcer in Côte d'Ivoire, B. trematum was a co-pathogen which was resistant to rifampicin and clarithromycin, unmatching M. ulcerans antibiotic susceptibility profile and counteracting the current treatment of Buruli ulcer in West Africa and Australia. Thus, we report here chronic mixed M. ulcerans-B. trematum chronic tropical ulcer as a specific form of Buruli ulcer in West Africa.
Topics: Humans; Mycobacterium ulcerans; Buruli Ulcer; Ulcer; Cote d'Ivoire; Skin Ulcer; Communicable Diseases
PubMed: 38060465
DOI: 10.1371/journal.pntd.0011413 -
Methods in Molecular Biology (Clifton,... 2022The oxidative phosphorylation (OxPhos) pathway has emerged as an attractive pathway for the development of anti-mycobacterial drugs. The OxPhos pathway is essential for...
The oxidative phosphorylation (OxPhos) pathway has emerged as an attractive pathway for the development of anti-mycobacterial drugs. The OxPhos pathway is essential for ATP resynthesis and maintenance of the electrochemical transmembrane gradient. The bioenergetic parameters of the pathway such as oxygen consumption rate and ATP levels are quantifiable using current technology. Measuring these parameters are useful tools to gauge rapidly the impact of drug candidates on their capacity to inhibit the OxPhos pathway in Mycobacterium ulcerans.
Topics: Adenosine Triphosphate; Buruli Ulcer; Energy Metabolism; Humans; Mycobacterium ulcerans
PubMed: 34643916
DOI: 10.1007/978-1-0716-1779-3_21 -
Lancet (London, England)
Topics: Africa; History, 20th Century; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Rain; Temperature
PubMed: 10609856
DOI: 10.1016/S0140-6736(05)77082-3 -
Australian Veterinary Journal Mar 2010Two horses were diagnosed as having Mycobacterium ulcerans infections. The first was a 21-year-old Quarterhorse-cross mare living in Mallacoota (a coastal town near the... (Review)
Review
Two horses were diagnosed as having Mycobacterium ulcerans infections. The first was a 21-year-old Quarterhorse-cross mare living in Mallacoota (a coastal town near the border of New South Wales and Victoria, Australia) that presented with lichenification, hair-loss and oedema on a fetlock, which subsequently ulcerated, as well as a non-healing ulcer on the wither. The second horse was a 32 year-old Standardbred gelding from Nicholson, near Bairnsdale, Victoria, that had an ulcerated lesion on its caudal thigh. Histologically, there were characteristic changes seen with M. ulcerans infections in other species, including extensive necrosis without associated granulomatous inflammation. The organisms were seen in Ziehl-Neelsen-stained smears or sections of the lesions from both horses and were isolated in culture from the first horse. A definitive diagnosis was provided by real-time polymerase chain reaction targeting the M. ulcerans-specific insertion sequence, IS2404. Delayed identification of the infectious agent in the first case led to the use of suboptimal antimicrobial therapy, resulting in failure to control the infection and the horse was subsequently euthanased. The second horse was successfully treated following surgical debulking of the centre of the lesion and one session of aggressive cryosurgery. Mycobacterium ulcerans should be considered in the differential diagnosis of unexplained lichenification with oedematous and ulcerated skin lesions in horses living in regions where this organism is endemic.
Topics: Animals; Anti-Bacterial Agents; Combined Modality Therapy; Fatal Outcome; Female; Horse Diseases; Horses; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Polymerase Chain Reaction; South Australia; Treatment Outcome; Victoria
PubMed: 20402694
DOI: 10.1111/j.1751-0813.2009.00544.x -
Lancet (London, England) Sep 2003Mycobacterium ulcerans causes devastating necrotic lesions in affected individuals. The disease, commonly called Buruli ulcer, is increasing in prevalance in western... (Review)
Review
CONTEXT
Mycobacterium ulcerans causes devastating necrotic lesions in affected individuals. The disease, commonly called Buruli ulcer, is increasing in prevalance in western African countries. Treatment is mainly surgical; no clinical trials have been done to support the use of antimycobacterial drugs. A secreted polyketide toxin, mycolactone, is responsible for the tissue damage; its chemical structure has been elucidated.
STARTING POINT
Although the main treatment is surgical, many patients with Buruli ulcer present late because of unusual beliefs about the disease and its treatment. Isabelle Aujoulat and colleagues recently showed, in a study in southern Bénin, Africa (Trop Med Int Health 2003; 8: 750-59), that although the ulcer is well recognised, the cause is often seen as environmental or because of witchcraft. In addition, treatment is thought to be destructive, costly, and ineffective. WHERE NEXT? Antimycobacterial drug regimens that hold promise based on animal and preliminary human studies will soon be tested in large well-designed controlled clinical trials. Information gleaned from the genomic sequence of M ulcerans could be used to design more effective vaccines, or new drug targets (eg, that knock out the enzymes of M ulcerans that synthesise mycolactone species).
Topics: Africa; Anti-Bacterial Agents; Bacterial Toxins; Benin; Humans; Macrolides; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Prevalence; Witchcraft
PubMed: 14522538
DOI: 10.1016/S0140-6736(03)14417-0