History, biology and chemistry of Mycobacterium ulcerans infections (Buruli ulcer disease)

Chany, Anne‐Caroline; Tresse, Cédric; Casarotto, Virginie; Blanchard, Nicolas

doi:10.1039/c3np70068b

Cited by 53 publications

(49 citation statements)

References 214 publications

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“…86 The production and biological roles of structurally distinct mycolactones from pathogenic Mycobacterium species have been thoroughly reviewed. 87–89 In vivo testing of mycolactones A and B in guinea pigs resulted in lesions similar to the Buruli ulcers developed by humans infected with M. ulcerans . Despite the severity of Buruli ulcers, the extensive skins lesions are not accompanied by pain.…”

Section: Natural Products In Human Diseasementioning

confidence: 99%

Natural products as mediators of disease

et al. 2017

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Humans are walking microbial ecosystems, each harboring a complex microbiome with the genetic potential to produce a vast array of natural products. Recent sequencing data suggest that our microbial inhabitants are critical for maintaining overall health. Shifts in microbial communities have been correlated to a number of diseases including infections, inflammation, cancer, and neurological disorders. Some of these clinically and diagnostically relevant phenotypes are a result of the presence of small molecules, yet we know remarkably little about their contributions to the health of individuals. Here, we review microbe-derived natural products as mediators of human disease.

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Section: Natural Products In Human Diseasementioning

confidence: 99%

Natural products as mediators of disease

et al. 2017

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“…Neben der antioxidativen Wirkung vieler virulenzrelevanter Naturstoffe können diese auch menschliche Zellen schädigen. Einer der bekanntesten, hochtoxischen Virulenzfaktoren ist das Mycolacton A/B von Mycobacterium ulcerans 14. Hauptsächlich in armen und ländlichen Teilen Afrikas verbreitet, ruft das Bakterium die Krankheit Buruli ulcera hervor, bei der die Haut abstirbt.…”

Section: Polyenstruktur Schützt Bakterienunclassified

Wie Bakterien uns mit Naturstoffen krank machen

Prothiwa¹,

Szamosvári²,

Böttcher³

2015

Nachr Chem

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“…Mycolactone is an exotoxin produced by Mycobacterium ulcerans and the central causative agent behind the neglected tropical skin disease called Buruli ulcer (1). The main characteristics of Buruli ulcer disease are extensive tissue destruction (due to the cell death) and a surprisingly low level of pain or inflammation (2,3). The toxin is thought to be secreted in bacterial outer membrane vesicles and then delivered to host cells (4) where it is cytotoxic and immunosuppressive, disrupting various cellular functions such as cytoskeletal organization, cytokine and chemokine expression and other signaling cascades (5,6).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Mycolactone Toxin Membrane Permeation: Atomistic vs Coarse-Grained MARTINI Simulations

Aydin

Sun

Swanson

2018

Preprint

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Mycolactone, a cytotoxic and immunosuppressive macrolide produced by Mycobacterium ulcerans, is the central virulent factor in the skin disease Buruli ulcer. This multifunctional cytotoxin affects fundamental cellular processes such as cell adhesion, immune response and cell death by targeting various cellular structures. Developing effective diagnostics that target mycolactone has been challenging, potentially due to suspected interactions with lipophilic architectures, including membranes. To better understand the pathogenesis of Buruli ulcer disease, aid in the development of diagnostics, and learn how amphiphiles in general use lipid trafficking to navigate the host environment, we seek to understand the nature of mycolactone-membrane interactions. Herein we characterize how the two dominant isomers of mycolactone (A and B) interact with and permeate DPPC membranes with all-atom molecular dynamics simulations employing transition tempered metadynamics, and compare these results with those obtained by MARTINI coarse-grained simulations. Our all-atom simulations reveal that both isomers have a strong preference to associate with the membrane, although their mechanisms and energetics of membrane permeation differ slightly. Water molecules are found to play an important role in the permeation process. Although the MARTINI coarse-grained simulations give the correct free energy of membrane association, they fail to capture the mechanism of permeation and role of water during permeation as seen in all-atom simulations.

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History, biology and chemistry of Mycobacterium ulcerans infections (Buruli ulcer disease)

Cited by 53 publications

References 214 publications

Natural products as mediators of disease

Natural products as mediators of disease

Wie Bakterien uns mit Naturstoffen krank machen

Mechanism of Mycolactone Toxin Membrane Permeation: Atomistic vs Coarse-Grained MARTINI Simulations

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