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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 -
Microbial Pathogenesis Dec 2020Mycolactone-producing mycobacteria (MPM) form an intriguing group of environmental opportunistic pathogens of mammals and human patients in whom they cause cutaneous and...
Mycolactone-producing mycobacteria (MPM) form an intriguing group of environmental opportunistic pathogens of mammals and human patients in whom they cause cutaneous and subcutaneous ulcers known as "Buruli ulcer" when they occur in humans. We reviewed whole genome sequence data and ecological and phenotypic characteristics from 44 MPMs and closely related Mycobacterium marinum. This analysis indicated that all the 24 M. marinum isolates were delineated into seven taxa and our comprehensive, polyphasic taxonomic approach led to the proposal of delineating M. marinum genomospecies, 01-07. Likewise, 20 MPMs isolates were delineated into seven additional M. ulcerans genomospecies, 01-07. A taxonomic card explaining the ecology, hosts of isolation and the plasmid harboured is provided for each taxon.
Topics: Animals; Buruli Ulcer; Humans; Macrolides; Mycobacterium; Mycobacterium ulcerans
PubMed: 32702376
DOI: 10.1016/j.micpath.2020.104362 -
Future Science OA Mar 2023is the causative agent of Buruli ulcer - a necrotizing skin infection. As an environmental pathogen, it has developed stress response mechanisms for survival. Similar... (Review)
Review
is the causative agent of Buruli ulcer - a necrotizing skin infection. As an environmental pathogen, it has developed stress response mechanisms for survival. Similar to endospore formation in , it is likely that employs sporulation mechanisms for its survival and transmission. In this review, we modeled possible transmission routes and patterns of from the environment to its host. We provided insights into the evolution of and its genomic profiles. We discuss reservoirs of as an environmental pathogen and its environmental survival. We comprehensively discuss sporulation as a possible stress response mechanism and modelled endospore formation in . At last, we highlighted sporulation associated markers, which upon expression trigger endospore formation.
PubMed: 37026027
DOI: 10.2144/fsoa-2022-0044 -
Expert Review of Vaccines Oct 2022Buruli ulcer is one of the most common mycobacterial diseases usually affecting poorer populations in tropical and subtropical environments. This disease, caused by...
BACKGROUND
Buruli ulcer is one of the most common mycobacterial diseases usually affecting poorer populations in tropical and subtropical environments. This disease, caused by infection, has devastating effects for patients, with significant health and economic burden. Antibiotics are often used to treat affected individuals, but in most cases, surgery is necessary.
AREA COVERED
We present progress on Buruli ulcer vaccines and identify knowledge gaps in this neglected tropical disease.
EXPERT OPINION
The lack of appropriate infrastructure in endemic areas, as well as the severity of symptoms and lack of noninvasive treatment options, highlights the need for an effective vaccine to combat this disease. In terms of humoral immunity, it is vital to consider its significance and the magnitude to which it inhibits or slows down the progression of the disease. Only by answering these key questions will it be possible to tailor more appropriate vaccination and preventative provisions.
Topics: Anti-Bacterial Agents; Buruli Ulcer; Humans; Mycobacterium ulcerans; Vaccination
PubMed: 35962475
DOI: 10.1080/14760584.2022.2113514 -
ACS Infectious Diseases Feb 2024In the recent decade, scientific communities have toiled to tackle the emerging burden of drug-resistant tuberculosis (DR-TB) and rapidly growing opportunistic... (Review)
Review
In the recent decade, scientific communities have toiled to tackle the emerging burden of drug-resistant tuberculosis (DR-TB) and rapidly growing opportunistic nontuberculous mycobacteria (NTM). Among these, two neglected mycobacteria species of the Acinetobacter family, and , are the etiological agents of leprosy and Buruli ulcer infections, respectively, and fall under the broad umbrella of neglected tropical diseases (NTDs). Unfortunately, lackluster drug discovery efforts have been made against these pathogenic bacteria in the recent decade, resulting in the discovery of only a few countable hits and majorly repurposing anti-TB drug candidates such as telacebec (Q203), P218, and TB47 for current therapeutic interventions. Major ignorance in drug candidate identification might aggravate the dramatic consequences of rapidly spreading mycobacterial NTDs in the coming days. Therefore, this Review focuses on an up-to-date account of drug discovery efforts targeting selected druggable targets from both bacilli, including the accompanying challenges that have been identified and are responsible for the slow drug discovery. Furthermore, a succinct discussion of the all-new possibilities that could be alternative solutions to mitigate the neglected mycobacterial NTD burden and subsequently accelerate the drug discovery effort is also included. We anticipate that the state-of-the-art strategies discussed here may attract major attention from the scientific community to navigate and expand the roadmap for the discovery of next-generation therapeutics against these NTDs.
Topics: Humans; Mycobacterium ulcerans; Mycobacterium leprae; Buruli Ulcer; Mycobacterium
PubMed: 38295025
DOI: 10.1021/acsinfecdis.3c00371 -
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 -
Pathogens (Basel, Switzerland) Aug 2023Buruli ulcer (BU) is a bacterial skin infection that is caused by and mainly affects people who reside in the rural areas of Africa and in suburban and beach resort... (Review)
Review
Buruli ulcer (BU) is a bacterial skin infection that is caused by and mainly affects people who reside in the rural areas of Africa and in suburban and beach resort communities in Australia. The infection typically begins as a painless papule or nodule that gradually develops into a large ulcer that can cause substantial impairment, damaging soft tissues and even bones. Early detection and immediate treatment are crucial to preventing further tissue damage and any potential complications, although it is worth noting that access to proper therapeutic resources can be limited in certain areas. The most commonly used antibiotics for treating BU are rifampicin, streptomycin, and clarithromycin; efforts have recently been made to introduce new treatments that increase the effectiveness and adherence to therapy. This article presents the latest research and management strategies regarding BU, providing an updated and intriguing perspective on this topic.
PubMed: 37764896
DOI: 10.3390/pathogens12091088 -
One Health (Amsterdam, Netherlands) Dec 2021Buruli ulcer (BU), the second most common mycobacterial disease in West Africa, is a necrotizing skin disease that can lead to high morbidity in affected patients. The... (Review)
Review
Buruli ulcer (BU), the second most common mycobacterial disease in West Africa, is a necrotizing skin disease that can lead to high morbidity in affected patients. The disease is caused by whose major virulence factor is mycolactone. Although early infection can be treated with antibiotics, an effective preventative strategy is challenging due to unknown reservoir(s) and unresolved mode(s) of transmission. Further, disease occurrence in remote locations with limited access to health facilities further complicates disease burden and associated costs. We discuss here transmission hypotheses and investigations into environmental reservoirs and discuss successes and challenges of studying and Buruli ulcer across human, animal, and environmental interfaces. We argue that a One Health approach is needed to advance the understanding of transmission and designing management scenarios that prevent and respond to epidemics. Although previous work has provided significant insights into risk factors, epidemiology and clinical perspectives of disease, understanding the bacterial ecology, environmental niches and role of mycolactone in natural environments and during infection of the human host remains equally important to better understanding and preventing this mysterious disease.
PubMed: 34485670
DOI: 10.1016/j.onehlt.2021.100311 -
Microorganisms Jul 2022Nontuberculous mycobacteria (NTM) represent an important group of environmentally saprophytic and potentially pathogenic bacteria that can cause serious mycobacterioses...
Nontuberculous mycobacteria (NTM) represent an important group of environmentally saprophytic and potentially pathogenic bacteria that can cause serious mycobacterioses in humans and animals. The sources of infections often remain undetected except for soil- or water-borne, water-washed, water-based, or water-related infections caused by groups of the complex; and other NTM species, including infection, known as fish tank granuloma, and infection, which is described as a Buruli ulcer. NTM could be considered as water-borne, air-borne, and soil-borne pathogens (sapronoses). A lot of clinically relevant NTM species could be considered due to the enormity of published data on permanent, periodic, transient, and incidental sapronoses. Interest is currently increasing in mycobacterioses diagnosed in humans and husbandry animals (esp. pigs) caused by NTM species present in peat bogs, potting soil, garden peat, bat and bird guano, and other matrices used as garden fertilizers. NTM are present in dust particles and in water aerosols, which represent certain factors during aerogenous infection in immunosuppressed host organisms during hospitalization, speleotherapy, and leisure activities. For this Special Issue, a collection of articles providing a current view of the research on NTM-including the clinical relevance, therapy, prevention of mycobacterioses, epidemiology, and ecology-are addressed.
PubMed: 35893574
DOI: 10.3390/microorganisms10081516 -
Methods in Molecular Biology (Clifton,... 2021The extraction and separation of native mycobacterial proteins remain necessary for antigen discovery, elucidation of enzymes to improve rational drug design,...
The extraction and separation of native mycobacterial proteins remain necessary for antigen discovery, elucidation of enzymes to improve rational drug design, identification of physiologic mechanisms, use as reagents for diagnostics, and defining host immune responses. In this chapter, methods for the manipulation of whole mycobacterial cells and culture exudates are described in detail as these methods are the requisite first steps towards native protein isolation. Specifically, several methods for the inactivation of viable Mycobacterium tuberculosis along with qualification assays are provided, as this is key to safe manipulation of cell pastes for downstream processes. Next, the concentration of spent culture filtrate media in order to permit separation of soluble, secreted proteins is described followed by the separation of mycobacteria extracellular vesicles (MEV) from the remaining soluble proteins in spent media. We then describe the generation of whole-cell lysate and facile separation of lysate into subcellular fractions to afford cell wall, cell membrane, and cytosol-enriched proteins. Due to the hydrophobic nature of cell wall and cell membrane proteins, several extraction protocols to resolve protein subsets (such as extraction with urea and SDS) are also provided. Finally, methods for separation of hydrophobic and hydrophilic proteins from both whole-cell lysate and spent culture media are included. While these methods were optimized for the manipulation of Mycobacterium tuberculosis cells, they have been successfully applied to extract and isolate Mycobacterium leprae, Mycobacterium ulcerans, and Mycobacterium avium proteins.
Topics: Bacterial Proteins; Cell Membrane; Membrane Proteins; Mycobacterium tuberculosis; Subcellular Fractions
PubMed: 34235649
DOI: 10.1007/978-1-0716-1460-0_3