scholarly journals Mycobacterium ulceranslow infectious dose and atypical mechanical transmission support insect bites and puncturing injuries in the spread of Buruli ulcer

2016 ◽  
Author(s):  
John R. Wallace ◽  
Kirstie M. Mangas ◽  
Jessica L. Porter ◽  
Renee Marcsisin ◽  
Sacha J. Pidot ◽  
...  
Keyword(s):  
Causative Agent ◽  
Disease Transmission ◽  
Buruli Ulcer ◽  
Blood Feeding ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Mechanical Transmission ◽  
Needle Puncture ◽  
Infectious Dose ◽  
Ulcer Disease

AbstractAddressing 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 notoscriptusandAedes aegypti) blood feeding or punctured with sterile needles. Two of 11 of mice withM. ulceranscontaminated tails exposed to feedingA. notoscriptusmosquitoes developed BU. Eighteen of 20 mice subjected to contaminated tail needle puncture developed BU. Mouse tails coated only in bacteria did not develop disease. We observed a low infectious dose-50 of four colony-forming units and a median incubation time of 12 weeks, consistent with data from human infections. We have uncovered a highly efficient and biologically plausible atypical transmission mode of BU via natural or anthropogenic skin punctures.Author summaryBuruli ulcer is a neglected tropical disease caused by infection withMycobacterium ulcerans. Unfortunately, how people contract this disease is not well understood. Here we show for the first time using experimental infections in mice that a very low dose ofM. ulceransdelivered beneath the skin by a minor injury caused by a blood-feeding insect (mosquito) or a needle puncture is sufficient to cause Buruli ulcer. This research provides important laboratory evidence to advance our understanding of Buruli ulcer disease transmission.

scholarly journals Mycobacterium ulceransin Mosquitoes and March flies captured from endemic areas of Northern Queensland, Australia

2018 ◽  
Author(s):  
Avishek Singh ◽  
William John Hannan McBride ◽  
Brenda Govan ◽  
Mark Pearson ◽  
Scott A. Ritchie
Keyword(s):  
Causative Agent ◽  
Buruli Ulcer ◽  
Mycobacterial Infection ◽  
Blood Feeding ◽  
Mycobacterium Ulcerans ◽  
Mechanical Transmission ◽  
Environmental Reservoir ◽  
Nontuberculous Mycobacterial Infection ◽  
Mode Of Transmission ◽  
Endemic Areas

AbstractMycobacterium ulceransis the causative agent of Buruli ulcer (BU). This nontuberculous mycobacterial infection has been reported in over 33 countries worldwide. In Australia, the majority of cases of BU have been recorded in coastal Victoria and the Mossman-Daintree areas of north Queensland. Mosquitoes have been postulated as a vector ofM. ulceransin Victoria, however the specific mode of transmission of this disease is still far from being well understood. In the current study, we trapped and analysed 16,900 (allocated to 845 pools) mosquitoes and 296 March flies from the endemic areas of north Queensland to examine for the presence ofM. ulceransDNA by polymerase chain reaction. Seven of 845 pools of mosquitoes were positive on screening using the IS2404 PCR target but only one pool was positive for presence ofM. ulceransafter confirmatory testing. None of the March fly samples were positive for the presence ofM. ulcerans.M. ulceranswas detected on proboscises of deliberately exposed mosquitoes.Author SummaryThe causative agent of Buruli ulcer is Mycobacterium ulcerans. This destructive skin disease is characterized by extensive and painless necrosis of skin and underlying tissues usually on extremities of body due to production of toxin named mycolactone. The disease is prevalent in Africa and coastal Australia. The exact mode of transmission and potential environmental reservoir for the pathogen still remain obscure. Aquatic and biting insects have been identified as important niche in transmission and maintenance of pathogen in the environment. In this study we screened mosquitoes and march flies captured from endemic areas of northern Queensland for the presence ofM. ulcerans.In addition, we conducted artificial blood feeding experiment to identify the role of mosquitoes in transmission of this pathogen. We found one pool of mosquito out of 845 pools positive forM. ulceransand none of the March fly samples were positive. This could indicate a low burden of the bacteria in the environment coinciding with a comparatively low number of human cases ofM. ulceransinfection seen during the trapping period of the study. Evidence to support mechanical transmission via mosquito proboscises was found.

scholarly journals Mycobacterium ulcerans low infectious dose and mechanical transmission support insect bites and puncturing injuries in the spread of Buruli ulcer

2017 ◽  
Vol 11 (4) ◽  
pp. e0005553 ◽  
Author(s):  
John R. Wallace ◽  
Kirstie M. Mangas ◽  
Jessica L. Porter ◽  
Renee Marcsisin ◽  
Sacha J. Pidot ◽  
...  
Keyword(s):  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Mechanical Transmission ◽  
Infectious Dose ◽  
Insect Bites

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 Molecular Mechanisms Underpinning the Circulation and Cellular Uptake of Mycobacterium ulcerans Toxin Mycolactone

2021 ◽  
Vol 12 ◽  
Author(s):  
Bruno Tello Rubio ◽  
Florence Bugault ◽  
Blandine Baudon ◽  
Bertrand Raynal ◽  
Sébastien Brûlé ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Molecular Mechanisms ◽  
Scavenger Receptor ◽  
Buruli Ulcer ◽  
Systemic Circulation ◽  
Mycobacterium Ulcerans ◽  
Host Cells ◽  
Ulcer Disease ◽  
Major Mechanism ◽  
Specific Association

Mycolactone is a diffusible lipid toxin produced by Mycobacterium ulcerans, the causative agent of Buruli ulcer disease. Altough bacterially derived mycolactone has been shown to traffic from cutaneous foci of infection to the bloodstream, the mechanisms underpinning its access to systemic circulation and import by host cells remain largely unknown. Using biophysical and cell-based approaches, we demonstrate that mycolactone specific association to serum albumin and lipoproteins is necessary for its solubilization and is a major mechanism to regulate its bioavailability. We also demonstrate that Scavenger Receptor (SR)-B1 contributes to the cellular uptake of mycolactone. Overall, we suggest a new mechanism of transport and cell entry, challenging the dogma that the toxin enters host cells via passive diffusion.

scholarly journals Buruli Ulcer: Review of a Neglected Skin Mycobacterial Disease

2017 ◽  
Vol 56 (4) ◽  
Author(s):  
Jeannette Guarner
Keyword(s):  
Clinical Presentation ◽  
Oral Treatment ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Tissue Necrosis ◽  
Content Type ◽  
Skin Nodule ◽  
The World ◽  
Health Organization

ABSTRACTBuruli ulcer is caused byMycobacterium ulcerans. This neglected disease occurs in scattered foci around the world, with a higher concentration of cases in West Africa. The mycobacteria produce mycolactones that cause tissue necrosis. The disease presents as a painless skin nodule that ulcerates as necrosis expands. Finding acid-fast bacilli in smears or histopathology, culturing the mycobacteria, and performingM. ulceransPCR in presumptive cases confirm the diagnosis. Medical treatment with oral rifampin and intramuscular streptomycin or oral treatment with rifampin plus clarithromycin for 8 weeks is supported by the World Health Organization. This review summarizes the epidemiology, pathogenesis, clinical presentation, diagnostic tests, and advances in treatment.

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.

Associations Between Mycobacterium ulcerans and Aquatic Plant Communities of West Africa: Implications for Buruli Ulcer Disease

EcoHealth ◽  
2014 ◽  
Vol 11 (2) ◽  
pp. 184-196 ◽  
Author(s):  
Mollie McIntosh ◽  
Heather Williamson ◽  
M. Eric Benbow ◽  
Ryan Kimbirauskas ◽  
Charles Quaye ◽  
...  
Keyword(s):  
West Africa ◽  
Plant Communities ◽  
Aquatic Plant ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Ulcer Disease

scholarly journals Molecular characterization of Mycobacterium ulcerans DNA gyrase and identification of mutations reduced susceptibility against quinolones in vitro

2021 ◽  
Author(s):  
Hyun Kim ◽  
Shigtarou Mori ◽  
Tsuyoshi Kenri ◽  
Yasuhiko Suzuki
Keyword(s):  
Buruli Ulcer ◽  
Dna Gyrase ◽  
Resistance Mechanisms ◽  
Docking Studies ◽  
Mycobacterium Ulcerans ◽  
Amino Acid Residues ◽  
Wild Type Enzyme ◽  
Ulcer Disease

ABSTRACTBuruli ulcer disease is a neglected necrotizing and disabling cutaneous tropical illness caused by Mycobacterium ulcerans (Mul). Fluoroquinolone (FQ), used in the treatment of this disease, has been known to act by inhibiting the enzymatic activities of DNA gyrase; however, the detailed molecular basis of these characteristics and the FQ resistance mechanisms in Mul remains unknown. This study investigated the detailed molecular mechanism of Mul DNA gyrase and the contribution of FQ resistance in vitro using recombinant proteins from the Mul subsp. shinshuense and Agy99 strains with reduced sensitivity to FQs. The IC50 of FQs against Ala91Vla and Asp95Gly mutants of Mul shinshuense and Agy99 GyrA subunits were 3.7- to 42.0-fold higher than those against wild-type enzyme. Similarly, the CC25 was 10- to 210-fold higher than those for the WT enzyme. Furthermore, the interaction between the amino acid residues of WT/mutant Mul DNA gyrase and FQ side chains was assessed via molecular docking studies. This is the first detailed study showing the contribution of Mul DNA GyrA subunit mutations to reduce the susceptibility against FQs.

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