Photodegradation of the Mycobacterium ulcerans Toxin, Mycolactones: Considerations for Handling and Storage

Marion, Estelle; Prado, Soizic; Cano, Camille; Babonneau, Jérèmie; Ghamrawi, Sarah; Marsollier, Laurent

doi:10.1371/journal.pone.0033600

Cited by 33 publications

(37 citation statements)

References 25 publications

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“…ulcerans strains and inoculation M. ulcerans strain nos. 01G897, JKD8083, and S4018 were originally isolated from patients from French Guiana, Australia, and Benin, respectively (22)(23)(24). Bacterial suspensions were prepared as previously described (10), and then adjusted at 2 3 10 5 acid-fast bacilli/ml to be inoculated (50 ml) into the tail of 6-wk-old females of the consanguine BALB/c, C57BL/6, and FVB/N mouse strains (Charles River Laboratories, Saint-Germain-Nuelles, France).…”

Section: Ethics Statement For Animal Experimentsmentioning

confidence: 99%

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FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer

Marion

Jarry

Cano

et al. 2016

The Journal of Immunology

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Buruli ulcer, a debilitating disease, is caused by Mycobacterium ulcerans. The incidence of this neglected tropical disease is steadily increasing. As a rule, without treatment, skin ulcers occur and a lengthy healing process may be observed associated with severe functional disabilities. Mouse models are already available to study establishment of lesions or evaluation of therapy but a lack of a suitable animal model, mimicking all clinical stages, in particular the healing process, remains an obstacle to understand the pathophysiology of M. ulcerans infection. M. ulcerans was s.c. inoculated in three consanguine mouse strains, that is, BALB/c and C57BL/6, classically used to study mycobacterial infection, and FVB/N. Strikingly, FVB/N mice, although as sensitive as all other mouse strains with respect to M. ulcerans infection, presented a spontaneous healing after the ulcerative phase despite stable bacterial load, and mycolactone toxin was not detected in the healed tissues. The spontaneous healing process was accompanied by an activation of the innate immune system. The adaptive response initiated by FVB/N mice was not involved in the healing process and did not confer protection against M. ulcerans. Our work highlights the importance of innate immune responses to control M. ulcerans infection. This in vivo model of M. ulcerans infection now paves the way for new avenues of research toward the elucidation of critical stages of this disease, such as the characterization of the regulation of mycolactone production, a better understanding of the pathophysiology of M. ulcerans infection, and the development of new therapeutic strategies.

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Section: Ethics Statement For Animal Experimentsmentioning

confidence: 99%

“…The organic phase was dried and phospholipids were precipitated with ice-cold acetone. Then, mycolactone was quantified by HPLC as previously described (23).…”

Section: Quantification Of Mycolactone In Tissuesmentioning

confidence: 99%

FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer

Marion

Jarry

Cano

et al. 2016

The Journal of Immunology

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“…IS 2404 , IS 2606 and KR-B based real-time PCR was used to identify the colonies used for the experiments (8). Mycolactones were prepared from M. ulcerans CU001 cells as previously described (9,10). Briefly, inactivated colonies were suspended in chloroform-methanol (2:1, v/v).…”

Section: Methodsmentioning

confidence: 99%

Mycolactone-independent pathogenicity ofMycobacterium ulcerans: an experimental study in plants

Bouam

Drancourt

2019

Preprint

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Mycobacterium ulcerans, the etiologic agent of Buruli ulcer in humans and animals, secretes macrolide exotoxins mycolactones which damage tissues after a cascade of cellular effects. M. ulcerans, an environmental organism with still elusive reservoirs and sources has been detected in soil and water in endemic areas where it could be in contact with plants. Symptom observations, microscopy and molecular biology were used to investigate M. ulcerans contact with plants in an experimental model mimicking the known pathology of Buruli ulcer in humans. Solanum lycopereum (tomato) plants with scarified or intact roots were transplanted into pots containing contaminated soil with M. ulcerans or a mixture of mycolactones A/B and C in the presence of negative control groups. Whereas plants with intact roots remained asymptomatic, M. ulcerans-infected plants with scarified roots had significantly more diseased leaves than controls (p = 0.004). Optic microscopy examination showed significantly more mycobacteria in the secondary and main roots than in controls (p=0.0008). Real-time PCRs detected M. ulcerans DNA in 7/12 (58%) of infected root samples versus none in the control plants (p = 0.04). Further study of plants with mycolactones A/B and C yielded no significant difference with negative controls. These results suggest that in this model, M. ulcerans exhibits a mycolactone-independent pathogenicity whose mechanism remains to be elucidated.

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“…As noted prior as, the optimal storage conditions for the archival of mycolactone was recently published. 112 Based upon these findings, our decision to store our mycolactone stocks as thin films should be reviewed. In light of the thin film stability studies I believe many of the variations observed through our purification and analysis effort were likely a product of the thin film and not wholly associated with photoablative effects, especially in the laboratory.…”

Section: Mycolactone Conclusion and Discussionmentioning

confidence: 99%

“…Several laboratories (including our own) have noted the instability of isolated mycolactone. 112 In collaboration with the Britton laboratory we further investigated the effects of natural and UV light on mycolactone stability and sought to evaluate the potential clinical relevance of such findings as a low cost approach to remediate the effects of mycolactone toxification. While our collaborators 113 were primarily concerned with the in-vivo and in-vitro modeling of mycolactone photoablation, our laboratory aims were to isolate sufficient quantities of mycolactone and study the effects of UV and visible photo irradiation on the chemical composition of the toxin.…”

Section: Introduction To Mycobacteria Ulceransmentioning

confidence: 99%

High Resolution Mass Spectrometry (HRMS) Based Investigation of Small Molecule, Bioactive Secondary Metabolites as Probes in the Examination of Bacterial Resistance and Virulence

Scarborough¹

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The widespread availability of antimicrobial chemotherapeutics over the last half of the twentieth century has offered dramatic increases in life expectancy. Unfortunately, many pathogenic agents are exhibiting ever increasing resistance to many frontline antibiotics. New chemotherapeutic agents are urgently needed to combat this threat; this work seeks to illustrate applications in which mass spectrometric techniques may be applied to the investigation of novel, small molecule chemotherapeutics for the treatment of bacterial infections. Chapter 1 contains an introduction to mass spectrometry, as well as an overview of relevant chromatographic techniques. Chapter 2 introduces the bacterium F tularensis and M ulcerans and details the MS based investigation of their secreted virulence factors. Chapter 3 introduces a human pathogen of particular concern, M tuberculosis, and contains a detailed reporting on the MS based investigation of internally synthesized compounds for the treatment of latent Tb. vii TABLE OF CONTENTS CHAPTER 1. INTRODUCTION TO MASS SPECTROMETERY .

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Photodegradation of the Mycobacterium ulcerans Toxin, Mycolactones: Considerations for Handling and Storage

Cited by 33 publications

References 25 publications

FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer

FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer

Mycolactone-independent pathogenicity ofMycobacterium ulcerans: an experimental study in plants

High Resolution Mass Spectrometry (HRMS) Based Investigation of Small Molecule, Bioactive Secondary Metabolites as Probes in the Examination of Bacterial Resistance and Virulence

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