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Biology of the Cell Nov 2018Infection with Mycobacterium ulcerans results in a necrotising skin disease known as a Buruli ulcer, the pathology of which is directly linked to the bacterial... (Review)
Review
Infection with Mycobacterium ulcerans results in a necrotising skin disease known as a Buruli ulcer, the pathology of which is directly linked to the bacterial production of the toxin mycolactone. Recent studies have identified the protein translocation machinery of the endoplasmic reticulum (ER) membrane as the primary cellular target of mycolactone, and shown that the toxin binds to the core subunit of the Sec61 complex. Mycolactone binding strongly inhibits the capacity of the Sec61 translocon to transport newly synthesised membrane and secretory proteins into and across the ER membrane. Since the ER acts as the entry point for the mammalian secretory pathway, and hence regulates initial access to the entire endomembrane system, mycolactone-treated cells have a reduced ability to produce a range of proteins including secretory cytokines and plasma membrane receptors. The global effect of this molecular blockade of protein translocation at the ER is that the host is unable to mount an effective immune response to the underlying mycobacterial infection. Prolonged exposure to mycolactone is normally cytotoxic, since it triggers stress responses activating the transcription factor ATF4 and ultimately inducing apoptosis.
Topics: Animals; Buruli Ulcer; Endoplasmic Reticulum; Humans; Macrolides; Models, Biological; Mycobacterium ulcerans; Protein Transport; SEC Translocation Channels
PubMed: 30055020
DOI: 10.1111/boc.201800030 -
PLoS Neglected Tropical Diseases Sep 2018Buruli ulcer has been increasing in incidence in southeastern Australia with unclear transmission mechanisms. We aimed to investigate the link between rainfall and case...
BACKGROUND
Buruli ulcer has been increasing in incidence in southeastern Australia with unclear transmission mechanisms. We aimed to investigate the link between rainfall and case numbers in two endemic areas of the state of Victoria; the Bellarine and Mornington Peninsulas.
METHODOLOGY
We created yearly and monthly graphs comparing rainfall with local Buruli ulcer incidence for the period 2004-2016 by endemic region and then considered a range of time lag intervals of 0-24 months to investigate patterns of correlation.
CONCLUSIONS
Optimal positive correlation for the Bellarine Peninsula occurred with a 12-month prior rainfall lag, however, no significant correlation was observed on the Mornington Peninsula for any time lag. These results provide an update in evidence to further explore transmission mechanisms which may differ between these geographically proximate endemic regions.
Topics: Buruli Ulcer; Humans; Incidence; Meteorological Concepts; Rain; Retrospective Studies; Time Factors; Victoria
PubMed: 30222751
DOI: 10.1371/journal.pntd.0006757 -
International Journal of Environmental... 2023is an environmental bacterium responsible for Buruli ulcer. This disease has a high frequency index in humid tropical regions, with a high incidence in Sub-Saharan...
UNLABELLED
is an environmental bacterium responsible for Buruli ulcer. This disease has a high frequency index in humid tropical regions, with a high incidence in Sub-Saharan Africa. The ecology and mode of transmission of this disease is not well established. Based on dilution effect hypothesis, acting as lowering disease transmission due to greater biodiversity, floristic inventory was carried out in the Health Districts of Daloa and Bouaké in Côte d'Ivoire. In each district, high and low endemic sites were investigated. A total of 169 plant species were inventoried for both low and high endemicity of Buruli ulcer sites in the districts. The Indval index revealed that 13 plant species were good indicators for Buruli ulcer highly endemic areas. The plants which correlate with high endemicity area were and For low endemic sites, a strong relationship was recorded for 37 plants. The indices revealed low similarity between high and low endemicity sites. Low endemicity sites expressed the highest plant species diversity. These results suggest the hypothesis that floristic richness is more important in sites of low endemicity than in those of high endemicity. Moreover, we observed a co-occurrence of some plant species and Buruli ulcer endemicity. This finding may lead to the fact that it is important to care about the biodiversity to prevent outbreak of Buruli ulcer cases.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s41742-023-00520-2.
PubMed: 37128551
DOI: 10.1007/s41742-023-00520-2 -
Antimicrobial Agents and Chemotherapy Aug 2020A single dose of Q203 (Telacebec), a phase 2 clinical candidate for tuberculosis, eradicates in a mouse model of Buruli ulcer infection without relapse up to 19 weeks...
A single dose of Q203 (Telacebec), a phase 2 clinical candidate for tuberculosis, eradicates in a mouse model of Buruli ulcer infection without relapse up to 19 weeks posttreatment. Clinical use of Q203 may dramatically simplify the clinical management of Buruli ulcer, a neglected mycobacterial disease.
Topics: Animals; Buruli Ulcer; Disease Models, Animal; Mice; Mycobacterium ulcerans; Tuberculosis
PubMed: 32631818
DOI: 10.1128/AAC.00727-20 -
Perceived water-related risk factors of Buruli ulcer in two villages of south-central Côte d'Ivoire.PLoS Neglected Tropical Diseases Dec 2022Buruli ulcer, caused by Mycobacterium ulcerans, is a neglected tropical skin disease that is primarily endemic in West and Central Africa, including Côte d'Ivoire....
BACKGROUND
Buruli ulcer, caused by Mycobacterium ulcerans, is a neglected tropical skin disease that is primarily endemic in West and Central Africa, including Côte d'Ivoire. Studies indicate that M. ulcerans infections are caused by contact with an environmental reservoir of the bacteria, governed by specific human biological conditions. Yet, the nature of this reservoir and the exact mode of transmission remain unknown.
METHODOLOGY
To identify ecologic risk factors of Buruli ulcer in south-central Côte d'Ivoire, we pursued a qualitative study matched with geo-referencing inquiry. Embedded in a broader integrated wound management research project, we (i) mapped households and water sources of laboratory confirmed Buruli ulcer cases and (ii) interviewed 12 patients and four health care workers to assess exposure to surface water and to deepen the understanding of perceived transmission pathways.
PRINCIPAL FINDINGS
Water availability, accessibility, and affordability were reported as key determinants for choosing water resources. Furthermore, perceived risks were related to environmental, structural, and individual factors. Despite the presence of improved water sources (e.g., drilled wells), communities heavily relied on unprotected surface water for a multitude of activities. The nearby Bandama River and seasonal waterbodies were frequently used for washing, bathing, and collection of water for drinking and cooking. Many residents also reported to cross the river on a daily basis for agricultural chores, and hence, are exposed to stagnant water during farming activities.
CONCLUSIONS/SIGNIFICANCE
Our study in two Buruli ulcer endemic villages in south-central Côte d'Ivoire revealed a wide range of water-related domestic activities that might expose people to an increased risk of contracting the disease. Environmental, biological, social, and cultural risk factors are closely interlinked and should be considered in future investigations of Buruli ulcer transmission. Active participation of the communities is key to better understand their circumstances to advance research and fight against Buruli ulcer and other neglected tropical diseases.
Topics: Humans; Buruli Ulcer; Water; Cote d'Ivoire; Mycobacterium ulcerans; Neglected Diseases; Risk Factors
PubMed: 36516125
DOI: 10.1371/journal.pntd.0010927 -
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 -
Microbes and Infection Jul 2011Buruli ulcer is a neglected disease caused by Mycobacterium ulcerans and represents the world's third most common mycobacterial infection. It produces the polyketide... (Review)
Review
Buruli ulcer is a neglected disease caused by Mycobacterium ulcerans and represents the world's third most common mycobacterial infection. It produces the polyketide toxins, mycolactones A, B, C and D, which induce apoptosis and necrosis. Clinical symptoms are subcutaneous nodules, papules, plaques and ulcerating oedemae, which can enlarge and destroy nerves and blood vessels and even invade bones by lymphatic or haematogenous spread (osteomyelitis). Patients usually do not suffer from pain or systematic inflammation. Surgery is the treatment of choice, although recurrence is common and wide surgical excisions including healthy tissues result in significant morbidity. Antibiotic therapy with rifamycins, aminoglycosides, macrolides and quinolones also improves cure rates. Still less exploited treatment options are phytochemicals from medicinal plants used in affected countries. Vaccination against Buruli ulcer is still in its infancy.
Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Apoptosis; Bacterial Proteins; Bacterial Toxins; Bacterial Vaccines; Buruli Ulcer; Chaperonin 60; Humans; Macrolides; Mycobacterium ulcerans; Necrosis; Neglected Diseases; Phytotherapy; Quinolones; Rifamycins; Vaccination; Vaccines, DNA
PubMed: 20832501
DOI: 10.1016/j.micinf.2010.09.002 -
The Journal of Infectious Diseases Nov 2023Mycobacterium ulcerans causes Buruli ulcer, the third most frequent mycobacterial disease after tuberculosis and leprosy. Transient clinical deteriorations, known as...
Mycobacterium ulcerans causes Buruli ulcer, the third most frequent mycobacterial disease after tuberculosis and leprosy. Transient clinical deteriorations, known as paradoxical reactions (PRs), occur in some patients during or after antibiotic treatment. We investigated the clinical and biological features of PRs in a prospective cohort of 41 patients with Buruli ulcer from Benin. Neutrophil counts decreased from baseline to day 90, and interleukin 6 (IL-6), granulocyte colony-stimulating factor, and vascular endothelial growth factor were the cytokines displaying a significant monthly decrease relative to baseline. PRs occurred in 10 (24%) patients. The baseline biological and clinical characteristics of the patients presenting with PRs did not differ significantly from those of the other patients. However, the patients with PRs had significantly higher IL-6 and tumor necrosis factor alpha (TNF-α) concentrations on days 30, 60, and 90 after the start of antibiotic treatment. The absence of a decrease in IL-6 and TNF-α levels during treatment should alert clinicians to the possibility of PR onset.
Topics: Humans; Buruli Ulcer; Prospective Studies; Tumor Necrosis Factor-alpha; Interleukin-6; Vascular Endothelial Growth Factor A; Anti-Bacterial Agents
PubMed: 37221015
DOI: 10.1093/infdis/jiad176 -
Emerging Infectious Diseases Jan 2011
Topics: Altitude; Benin; Buruli Ulcer; Endemic Diseases; Humans; Mycobacterium ulcerans; Population Surveillance; Prevalence; Risk Factors; Rural Population; Seasons
PubMed: 21192889
DOI: 10.3201/eid1701.100644 -
PLoS Neglected Tropical Diseases Jun 2018Buruli ulcer (BU), a necrotizing skin infection caused by Mycobacterium ulcerans is the third most important mycobacterial disease globally after tuberculosis and...
BACKGROUND
Buruli ulcer (BU), a necrotizing skin infection caused by Mycobacterium ulcerans is the third most important mycobacterial disease globally after tuberculosis and leprosy in immune competent individuals. This study reports on the retrospective analyses of microbiologically confirmed Buruli ulcer (BU) cases in seventy-five health facilities in Ghana.
METHOD/PRINCIPAL FINDINGS
Pathological samples were collected from BU lesions and transported either through courier services or by car directly to the laboratory. Samples were processed and analysed by IS2404 PCR, culture and Ziehl-Neelsen staining for detection of acid-fast bacilli. From 2008 to 2016, we analysed by PCR, 2,287 samples of 2,203 cases from seventy-five health facilities in seven regions of Ghana (Ashanti, Brong Ahafo, Central, Eastern, Greater Accra, Northern and Volta). The mean annual positivity rate was 46.2% and ranged between 14.6% and 76.2%. The yearly positivity rates from 2008 to 2016 were 52.3%, 76.2%, 56.7%, 53.8%, 41.2%, 41.5%, 22.9%, 28.5% and 14.6% respectively. Of the 1,020 confirmed cases, the ratio of female to male was 518 and 502 respectively. Patients who were 15 years of age and below accounted for 39.8% of all cases. The median age was 20 years (IQR = 10-43). Ulcerative lesions were 69.2%, nodule (9.6%), plaque (2.9%), oedema (2.5%), osteomyelitis (1.1%), ulcer/oedema (9.5%) and ulcer/plaque (5.2%). Lesions frequently occurred on the lower limbs (57%) followed by the upper limbs (38%), the neck and head (3%) and the least found on the abdomen (2%).
CONCLUSIONS/SIGNIFICANCE
Our findings show a decline in microbiological confirmed rates over the years and therefore call for intensive education on case recognition to prevent over-diagnosis as BU cases decline.
Topics: Adolescent; Adult; Buruli Ulcer; Child; Child, Preschool; Clinical Laboratory Techniques; Female; Ghana; Health Facilities; Humans; Infant; Infant, Newborn; Male; Middle Aged; Mycobacterium ulcerans; Osteomyelitis; Polymerase Chain Reaction; Retrospective Studies; Young Adult
PubMed: 29870529
DOI: 10.1371/journal.pntd.0006560