Glycopeptidolipid glycosylation controls surface properties and pathogenicity in Mycobacterium abscessus.

Daher, W; Leclercq, L-D; Johansen, MD; Hamela, C; Karam, J; Trivelli, X; Nigou, J; Guérardel, Y; Kremer, L

Glycopeptidolipid glycosylation controls surface properties and pathogenicity in Mycobacterium abscessus.

Daher, W Leclercq, L-D Johansen, MD Hamela, C Karam, J Trivelli, X Nigou, J Guérardel, Y Kremer, L

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Publisher:: Cell Press
Publication Type:: Journal Article
Citation:: Cell chemical biology, 2022, 29, (5), pp. 910-924
Issue Date:: 2022-05-19

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Field	Value	Language
dc.contributor.author	Daher, W
dc.contributor.author	Leclercq, L-D
dc.contributor.author	Johansen, MD
dc.contributor.author	Hamela, C
dc.contributor.author	Karam, J
dc.contributor.author	Trivelli, X
dc.contributor.author	Nigou, J
dc.contributor.author	Guérardel, Y
dc.contributor.author	Kremer, L
dc.date.accessioned	2022-12-14T02:08:31Z
dc.date.available	2022-03-10
dc.date.available	2022-12-14T02:08:31Z
dc.date.issued	2022-05-19
dc.identifier.citation	Cell chemical biology, 2022, 29, (5), pp. 910-924
dc.identifier.issn	2451-9448
dc.identifier.issn	2451-9448
dc.identifier.uri	http://hdl.handle.net/10453/164391
dc.description.abstract	Mycobacterium abscessus is an emerging and difficult-to-manage mycobacterial species that exhibits smooth (S) or rough (R) morphotypes. Disruption of glycopeptidolipid (GPL) production results in transition from S to R and severe lung disease. A structure-activity relationship study was undertaken to decipher the role of GPL glycosylation in morphotype transition and pathogenesis. Deletion of gtf3 uncovered the prominent role of the extra rhamnose in enhancing mannose receptor-mediated internalization of M. abscessus by macrophages. In contrast, the absence of the 6-deoxy-talose and the first rhamnose in mutants lacking gtf1 and gtf2, respectively, affected M abscessus phagocytosis but also resulted in the S-to-R transition. Strikingly, gtf1 and gtf2 mutants displayed a strong propensity to form cords and abscesses in zebrafish, leading to robust and lethal infection. Together, these results underscore the importance and differential contribution of GPL monosaccharides in promoting virulence and infection outcomes.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Cell Press
dc.relation.ispartof	Cell chemical biology
dc.relation.isbasedon	10.1016/j.chembiol.2022.03.008
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.mesh	Animals
dc.subject.mesh	Glycosylation
dc.subject.mesh	Mycobacterium abscessus
dc.subject.mesh	Rhamnose
dc.subject.mesh	Surface Properties
dc.subject.mesh	Virulence
dc.subject.mesh	Zebrafish
dc.subject.mesh	Animals
dc.subject.mesh	Glycosylation
dc.subject.mesh	Mycobacterium abscessus
dc.subject.mesh	Rhamnose
dc.subject.mesh	Surface Properties
dc.subject.mesh	Virulence
dc.subject.mesh	Zebrafish
dc.subject.mesh	Animals
dc.subject.mesh	Zebrafish
dc.subject.mesh	Rhamnose
dc.subject.mesh	Virulence
dc.subject.mesh	Glycosylation
dc.subject.mesh	Surface Properties
dc.subject.mesh	Mycobacterium abscessus
dc.title	Glycopeptidolipid glycosylation controls surface properties and pathogenicity in Mycobacterium abscessus.
dc.type	Journal Article
utslib.citation.volume	29
utslib.location.activity	United States
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2022-12-14T02:08:30Z
pubs.issue	5
pubs.publication-status	Published
pubs.volume	29
utslib.citation.issue	5

Abstract:

Mycobacterium abscessus is an emerging and difficult-to-manage mycobacterial species that exhibits smooth (S) or rough (R) morphotypes. Disruption of glycopeptidolipid (GPL) production results in transition from S to R and severe lung disease. A structure-activity relationship study was undertaken to decipher the role of GPL glycosylation in morphotype transition and pathogenesis. Deletion of gtf3 uncovered the prominent role of the extra rhamnose in enhancing mannose receptor-mediated internalization of M. abscessus by macrophages. In contrast, the absence of the 6-deoxy-talose and the first rhamnose in mutants lacking gtf1 and gtf2, respectively, affected M abscessus phagocytosis but also resulted in the S-to-R transition. Strikingly, gtf1 and gtf2 mutants displayed a strong propensity to form cords and abscesses in zebrafish, leading to robust and lethal infection. Together, these results underscore the importance and differential contribution of GPL monosaccharides in promoting virulence and infection outcomes.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/164391