scholarly journals Mycolactone Is Responsible for the Painlessness of Mycobacterium ulcerans Infection (Buruli Ulcer) in a Murine Study

2008 ◽  
Vol 76 (5) ◽  
pp. 2002-2007 ◽  
Author(s):  
Junichiro En ◽  
Masamichi Goto ◽  
Kazue Nakanaga ◽  
Michiyo Higashi ◽  
Norihisa Ishii ◽  
...  
Keyword(s):  
Buruli Ulcer ◽  
Pulmonary Hemorrhage ◽  
Nerve Damage ◽  
Mycobacterium Ulcerans ◽  
Nerve Degeneration ◽  
Limb Amputation ◽  
Cell Nuclei ◽  
Neutrophilic Infiltration ◽  
Sensory Recovery ◽  
Chronic Skin

ABSTRACT Buruli ulcer is a chronic skin disease caused by Mycobacterium ulcerans, which produces a toxic lipid mycolactone. Despite the extensive necrosis and tissue damage, the lesions are painless. This absence of pain prevents patients from seeking early treatment and, as a result, many patients experience severe sequelae, including limb amputation. We have reported that mice inoculated with M. ulcerans show loss of pain sensation and nerve degeneration. However, the molecules responsible for the nerve damage have not been identified. In order to clarify whether mycolactone alone can induce nerve damage, mycolactone A/B was injected to footpads of BALB/c mice. A total of 100 μg of mycolactone induced footpad swelling, redness, and erosion. The von Frey sensory test showed hyperesthesia on day 7, recovery on day 21, and hypoesthesia on day 28. Histologically, the footpads showed epidermal erosion, moderate stromal edema, and moderate neutrophilic infiltration up to day 14, which gradually resolved. Nerve bundles showed intraneural hemorrhage, neutrophilic infiltration, and loss of Schwann cell nuclei on days 7 and 14. Ultrastructurally, vacuolar change of myelin started on day 14 and gradually subsided by day 42, but the density of myelinated fibers remained low. This study demonstrated that initial hyperesthesia is followed by sensory recovery and final hypoesthesia. Our present study suggests that mycolactone directly damages nerves and is responsible for the absence of pain characteristic of Buruli ulcer. Furthermore, mice injected with 200 μg of mycolactone showed pulmonary hemorrhage. This is the first study to demonstrate the systemic effects of mycolactone.

scholarly journals Aquatic Snails, Passive Hosts of Mycobacterium ulcerans

2004 ◽  
Vol 70 (10) ◽  
pp. 6296-6298 ◽  
Author(s):  
Laurent Marsollier ◽  
Tchibozo Sévérin ◽  
Jacques Aubry ◽  
Richard W. Merritt ◽  
Jean-Paul Saint André ◽  
...  
Keyword(s):  
Buruli Ulcer ◽  
Indirect Evidence ◽  
Mycobacterium Ulcerans ◽  
Aquatic Environments ◽  
Potential Vector ◽  
Ulcer Disease ◽  
Skin Ulcers ◽  
Chronic Skin ◽  
Favorable Conditions ◽  
Water Bugs

ABSTRACT Accumulative indirect evidence of the epidemiology of Mycobacterium ulcerans infections causing chronic skin ulcers (i.e., Buruli ulcer disease) suggests that the development of this pathogen and its transmission to humans are related predominantly to aquatic environments. We report that snails could transitorily harbor M. ulcerans without offering favorable conditions for its growth and replication. A novel intermediate link in the transmission chain of M. ulcerans becomes likely with predator aquatic insects in addition to phytophage insects. Water bugs, such as Naucoris cimicoides, a potential vector of M. ulcerans, were shown to be infected specifically by this bacterium after feeding on snails experimentally exposed to M. ulcerans.

scholarly journals Skin-specific antibodies neutralizing mycolactone toxin during the spontaneous healing of Mycobacterium ulcerans infection

2020 ◽  
Vol 6 (9) ◽  
pp. eaax7781 ◽  
Author(s):  
Mélanie Foulon ◽  
Amélie Pouchin ◽  
Jérémy Manry ◽  
Fida Khater ◽  
Marie Robbe-Saule ◽  
...  
Keyword(s):  
Healing Process ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Immunomodulatory Activity ◽  
Spontaneous Healing ◽  
Specific Antibodies ◽  
Skin Ulcers ◽  
Chronic Skin ◽  
Health Organization

Buruli ulcer, a neglected tropical infectious disease, is caused by Mycobacterium ulcerans. Without treatment, its lesions can progress to chronic skin ulcers, but spontaneous healing is observed in 5% of cases, suggesting the possible establishment of a host strategy counteracting the effects of M. ulcerans. We reveal here a skin-specific local humoral signature of the spontaneous healing process, associated with a rise in antibody-producing cells and specific recognition of mycolactone by the mouse IgG2a immunoglobulin subclass. We demonstrate the production of skin-specific antibodies neutralizing the immunomodulatory activity of the mycolactone toxin, and confirm the role of human host machinery in triggering effective local immune responses by the detection of anti-mycolactone antibodies in patients with Buruli ulcer. Our findings pave the way for substantial advances in both the diagnosis and treatment of Buruli ulcer in accordance with the most recent challenges issued by the World Health Organization.

scholarly journals Role of mycolactone in the nerve damage of Buruli ulcer (Mycobacterium ulcerans infection)

2011 ◽  
Vol 80 (1) ◽  
pp. 5-10 ◽  
Author(s):  
Junichiro EN ◽  
Norihisa ISHII ◽  
Masamichi GOTO
Keyword(s):  
Buruli Ulcer ◽  
Nerve Damage ◽  
Mycobacterium Ulcerans

scholarly journals Aquatic Insects as a Vector for Mycobacterium ulcerans

2002 ◽  
Vol 68 (9) ◽  
pp. 4623-4628 ◽  
Author(s):  
Laurent Marsollier ◽  
Raymond Robert ◽  
Jacques Aubry ◽  
Jean-Paul Saint André ◽  
Henri Kouakou ◽  
...  
Keyword(s):  
Aquatic Insects ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Laboratory Mice ◽  
Healthy Humans ◽  
Skin Ulcers ◽  
Chronic Skin ◽  
Set Up ◽  
Aquatic Bugs

ABSTRACT Mycobacterium ulcerans is an emerging environmental pathogen which causes chronic skin ulcers (i.e., Buruli ulcer) in otherwise healthy humans living in tropical countries, particularly those in Africa. In spite of epidemiological and PCR data linking M. ulcerans to water, the mode of transmission of this organism remains elusive. To determine the role of aquatic insects in the transmission of M. ulcerans, we have set up an experimental model with aquariums that mimic aquatic microenvironments. We report that M. ulcerans may be transmitted to laboratory mice by the bite of aquatic bugs (Naucoridae) that are infected with this organism. In addition, M. ulcerans appears to be localized exclusively within salivary glands of these insects, where it can both survive and multiply without causing any observable damage in the insect tissues. Subsequently, we isolated M. ulcerans from wild aquatic insects collected from a zone in the Daloa region of Ivory Coast where Buruli ulcer is endemic. Taken together, these results point to aquatic insects as a possible vector of M. ulcerans.

scholarly journals Buruli Ulcer (Acha-ere): Pathogenesis and Manifestation

2019 ◽  
pp. 1-5
Author(s):  
Elendu C. Onwuchekwa ◽  
Uzochukwu G. Ekeleme ◽  
Oliver Onu-Osi ◽  
Okonudo P. Osezele
Keyword(s):  
Subcutaneous Tissue ◽  
Buruli Ulcer ◽  
Central Africa ◽  
Mycobacterium Ulcerans ◽  
Actin Dynamics ◽  
Tropical Regions ◽  
West And Central Africa ◽  
Chronic Skin ◽  
Pass Through ◽  
Syndrome Protein

Infection of subcutaneous tissue with Mycobacterium ulcerans can lead to chronic skin ulceration known as Buruli ulcer. It has been reported in over 33 countries around the world, the greatest burden of disease is in the tropical regions of West and Central Africa, Australia, and Japan. It primarily affects children aged 5-15 years. Buruli ulcers generally begin as a painless dermal papule or subcutaneous edematous nodule, which over a period of weeks to months, breaks down to form an extensive necrotic ulcer with undermined edges. The pathogenesis of this neglected tropical disease is dependent on a lipidlike toxin, mycolactone, which diffuses through tissue away from the infecting organisms and elucidate its cytotoxic and immunosuppressive properties. The underlying molecular targets for mycolactone are: First, it can target scaffolding proteins (such as Wiskott Aldrich Syndrome Protein), which control actin dynamics in adherent cells and therefore lead to detachment and cell death. Second, it prevents the co-translational translocation (and therefore production) of many proteins that pass through the endoplasmic reticulum for secretion or placement in cell membranes.  Treatment includes a prolonged course of antibiotics and surgical debridement. Early identification and treatment are key, as lesions heal with scarring that can be a significant source of morbidity.

Interactions between ecological and socio-economic drivers of Buruli ulcer burden in Sub-Saharan Africa: opportunities for an improved control

2018 ◽  
Author(s):  
Andes Garchitorena ◽  
Matthew H. Bonds ◽  
Jean-Francois Guégan ◽  
Benjamin Roche
Keyword(s):  
Socioeconomic Factors ◽  
Disease Transmission ◽  
Access To Health Care ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Sub Saharan Africa ◽  
Aquatic Environments ◽  
Human Populations ◽  
Complex Interactions ◽  
Sub Saharan

This chapter provides an overview of the complex interactions between ecological and socioeconomic factors for the development and control of Buruli ulcer in Sub-Saharan Africa. We review key ecological and evolutionary processes driving the environmental persistence and proliferation of Mycobacterium ulcerans, the causative agent, within aquatic environments, as well as transmission processes from these aquatic environments to human populations. We also outline key socioeconomic factors driving the economic and health burden of Buruli ulcer in endemic regions, revealed by reciprocal feedbacks between poverty, disease transmission from exposure aquatic environments and disease progression to severe stages owing to low access to health care. The implications of such insights for disease control, both in terms of limitations of current strategies and directions for the future, are discussed.

scholarly journals Cellular Immunity Confers Transient Protection in Experimental Buruli Ulcer following BCG or Mycolactone-Negative Mycobacterium ulcerans Vaccination

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e33406 ◽  
Author(s):  
Alexandra G. Fraga ◽  
Teresa G. Martins ◽  
Egídio Torrado ◽  
Kris Huygen ◽  
Françoise Portaels ◽  
...  
Keyword(s):  
Cellular Immunity ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans

scholarly journals Community-based geographical distribution of Mycobacterium ulcerans VNTR-genotypes from the environment and humans in the Nyong valley, Cameroon

2021 ◽  
Vol 49 (1) ◽  
Author(s):  
Francis Zeukeng ◽  
Anthony Ablordey ◽  
Solange E. Kakou-Ngazoa ◽  
Stephen Mbigha Ghogomu ◽  
David N’golo Coulibaly ◽  
...  
Keyword(s):  
Environmental Samples ◽  
Tandem Repeats ◽  
Buruli Ulcer ◽  
Variable Number ◽  
Mycobacterium Ulcerans ◽  
Community Based ◽  
Human Samples ◽  
Route Of Transmission ◽  
Mode Of Transmission ◽  
Animal Reservoirs

Abstract Background Genotyping is a powerful tool for investigating outbreaks of infectious diseases and it can provide useful information such as identifying the source and route of transmission, and circulating strains involved in the outbreak. Genotyping techniques based on variable number of tandem repeats (VNTR) are instrumental in detecting heterogeneity in Mycobacterium ulcerans (MU) and also for discriminating MU from other mycobacteria species. Here, we describe and map the distribution of MU genotypes in Buruli ulcer (BU) endemic communities of the Nyong valley in Cameroon. We also tested the hypothesis of whether the suspected animal reservoirs of BU that share the human microhabitat are shedding contaminated fecal matters and saliva into their surrounding environments. Methods Environmental samples from suspected MU-risk factors and lesion swabs from human patients were sampled in BU-endemic communities and tested for the presence of MU by qPCR targeting three independent sequences (IS2404, IS2606, KR-B). Positive samples to MU were further genotyped by VNTR with confirmation by sequencing of four loci (MIRU1, Locus 6, ST1, Locus 19). Results MU was detected in environmental samples including water bodies (23%), biofilms (14%), detritus (10%), and in human patients (73%). MU genotypes D, W, and C were found both in environmental and human samples. The micro geo-distribution of MU genotypes from communities showed that genotype D is found both in environmental and human samples, while genotypes W and C are specific to environmental samples and human lesions, respectively. No obvious focal grouping of MU genotypes was observed at the community scale. An additional survey in the human microhabitat suggests that domestic and wild animals do not shed MU in their saliva and feces in sampled communities. Conclusions VNTR typing uncovered different MU genotypes circulating in the endemic communities of the Akonolinga district. A MU environmental genotype was found in patients, yet the mechanism of contamination remains to be investigated; and recovering MU in culture from the environment remains key priority to enable a better understanding of the mode of transmission of BU. We also conclude that excretions from suspected animals are unlikely to be major sources of MU in the Nyong Valley in Cameroon.

scholarly journals Local Cellular Immune Responses and Pathogenesis of Buruli Ulcer Lesions in the Experimental Mycobacterium Ulcerans Pig Infection Model

2016 ◽  
Vol 10 (4) ◽  
pp. e0004678 ◽  
Author(s):  
Miriam Bolz ◽  
Nicolas Ruggli ◽  
Nicole Borel ◽  
Gerd Pluschke ◽  
Marie-Thérèse Ruf
Keyword(s):  
Immune Responses ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Infection Model ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Recent Advances in Biomarkers and Regenerative Medicine for Diabetic Neuropathy

2021 ◽  
Vol 22 (5) ◽  
pp. 2301
Author(s):  
Yoshikai Fujita ◽  
Tatsufumi Murakami ◽  
Akihiro Nakamura
Keyword(s):  
Diabetic Neuropathy ◽  
Target Gene ◽  
Pathological Condition ◽  
Nerve Fibers ◽  
Nerve Degeneration ◽  
Limb Amputation ◽  
Sensory Impairment ◽  
Mechanical Stimuli ◽  
Pathological Conditions ◽  
The Relationship

Diabetic neuropathy is one of the most common complications of diabetes. This complication is peripheral neuropathy with predominant sensory impairment, and its symptoms begin with hyperesthesia and pain and gradually become hypoesthesia with the loss of nerve fibers. In some cases, lower limb amputation occurs when hypoalgesia makes it impossible to be aware of trauma or mechanical stimuli. On the other hand, up to 50% of these complications are asymptomatic and tend to delay early detection. Therefore, sensitive and reliable biomarkers for diabetic neuropathy are needed for an early diagnosis of this condition. This review focuses on systemic biomarkers that may be useful at this time. It also describes research on the relationship between target gene polymorphisms and pathological conditions. Finally, we also introduce current information on regenerative therapy, which is expected to be a therapeutic approach when the pathological condition has progressed and nerve degeneration has been completed.

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