Pleiotropic molecular effects of the Mycobacterium ulcerans virulence factor mycolactone underlying the cell death and immunosuppression seen in Buruli ulcer

Hall, Belinda; Simmonds, Rachel

doi:10.1042/bst20130133

Cited by 52Mycobacterium research and diagnosisTuberculosis Research and EpidemiologyBurkholderia infections and melioidosis

Pleiotropic molecular effects of the Mycobacterium ulcerans virulence factor mycolactone underlying the cell death and immunosuppression seen in Buruli ulcer

Hall, Belinda, Simmonds, Rachel·2014·Biochemical Society Transactions

DOI 10.1042/bst20130133

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Abstract

Mycolactone is a polyketide macrolide lipid-like secondary metabolite synthesized by Mycobacterium ulcerans, the causative agent of BU (Buruli ulcer), and is the only virulence factor for this pathogen identified to date. Prolonged exposure to high concentrations of mycolactone is cytotoxic to diverse mammalian cells (albeit with varying efficiency), whereas at lower doses it has a spectrum of immunosuppressive activities. Combined, these pleiotropic properties have a powerful influence on local and systemic cellular function that should explain the pathophysiology of BU disease. The last decade has seen significant advances in our understanding of the molecular mechanisms underlying these effects in a range of different cell types. The present review focuses on the current state of our knowledge of mycolactone function, and its molecular and cellular targets, and seeks to identify commonalities between the different functional and cellular systems. Since mycolactone influences fundamental cellular processes (cell division, cell death and inflammation), getting to the root of how mycolactone achieves this could have a profound impact on our understanding of eukaryotic cell biology.

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Mycolactone inhibits phagocytosis and hampers phagolysosomal maturation in macrophages.
“This may be explained by the fact that mycolactone inhibits phagocytosis and hampers phagolysosomal maturation in macrophages (98, 99).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [99]
Mycolactone contributes to immunosuppression by hampering the production of several cytokines and chemokines from macrophages.
“In addition, mycolactone contributes to immunosuppression by hampering the production of several cytokines and chemokines from macrophages (Figure 2A) (99–101); mycolactone is effective at dampening the production of LPS-induced mediators.”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [99]
Mycolactone is effective at dampening the production of LPS-induced mediators.
“In addition, mycolactone contributes to immunosuppression by hampering the production of several cytokines and chemokines from macrophages (Figure 2A) (99–101); mycolactone is effective at dampening the production of LPS-induced mediators.”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [99]

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Authors: Hall, B., & Simmonds, R.
Affiliations: University of Surrey (GB)
Corresponding author: Hall, Belinda
Simmonds, Rachel
ORCID: Hall, Belinda
Simmonds, Rachel
Venue: Biochemical Society Transactions
Publisher: Portland Press Ltd.
Published: 2014-01-23
Volume: 42
Issue: 1
Pages: 177-183
ISSN: 0300-5127 (ISSN-L)
1470-8752
DOI: 10.1042/bst20130133
OpenAlex: W1965747027
Cited by: 52
References: 57
Citations by year: 2024: 3 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 4
FWCI: 0.89
Type: journal article
Language: en
Open access: closed
Locations: Biochemical Society Transactions (publishedVersion)
PubMed (publishedVersion)
Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
Funders: Wellcome Trust (WT080114MA)
Topics: Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
Health Sciences › Medicine › Epidemiology › Burkholderia infections and melioidosis
Keywords: mycolactone, Mycobacterium ulcerans, Buruli ulcer, virulence factors, cytotoxicity, cell death, immunosuppression, molecular targets, inflammation, cell division, eukaryotic cell biology
MeSH terms: Animals, Humans, Immune Tolerance, Immunity, Innate, Protein Biosynthesis, Apoptosis, Macrolides, Mycobacterium ulcerans, Virulence Factors, Buruli Ulcer, Host-Pathogen Interactions

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Pleiotropic molecular effects of the Mycobacterium ulcerans virulence factor mycolactone underlying the cell death and immunosuppression seen in Buruli ulcer

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