The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
09 Jul 2024
Historique:
received: 06 12 2023
accepted: 26 06 2024
medline: 10 7 2024
pubmed: 10 7 2024
entrez: 9 7 2024
Statut: epublish

Résumé

Mycobacterial glycolipids are important cell envelope structures that drive host-pathogen interactions. Arguably, the most important are lipoarabinomannan (LAM) and its precursor, lipomannan (LM), which are trafficked from the bacterium to the host via unknown mechanisms. Arabinomannan is thought to be a capsular derivative of these molecules, lacking a lipid anchor. However, the mechanism by which this material is generated has yet to be elucidated. Here, we describe the identification of a glycoside hydrolase family 76 enzyme that we term LamH (Rv0365c in Mycobacterium tuberculosis) which specifically cleaves α-1,6-mannoside linkages within LM and LAM, driving its export to the capsule releasing its phosphatidyl-myo-inositol mannoside lipid anchor. Unexpectedly, we found that the catalytic activity of this enzyme is important for efficient exit from stationary phase cultures, potentially implicating arabinomannan as a signal for growth phase transition. Finally, we demonstrate that LamH is important for M. tuberculosis survival in macrophages.

Identifiants

pubmed: 38982040
doi: 10.1038/s41467-024-50051-3
pii: 10.1038/s41467-024-50051-3
doi:

Substances chimiques

lipoarabinomannan 0
Lipopolysaccharides 0
Mannans 0
arabinomannan 53026-40-7
Glycoside Hydrolases EC 3.2.1.-
Bacterial Proteins 0
lipomannan 0
phosphatidylinositol mannoside 0
Phosphatidylinositols 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

5740

Subventions

Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/S010122/1
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/X00841X/1
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/X016749/1
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/W01954X/1
Organisme : Wellcome Trust (Wellcome)
ID : 226644/Z/22/Z
Organisme : Wellcome Trust (Wellcome)
ID : 209437/Z/17/Z
Organisme : Wellcome Trust (Wellcome)
ID : 226644/Z/22/Z
Organisme : Wellcome Trust (Wellcome)
ID : 226644/Z/22/Z
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/S000542/1
Organisme : Department of Education and Training | Australian Research Council (ARC)
ID : DP210100235
Organisme : Department of Education and Training | Australian Research Council (ARC)
ID : DP210100362
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : R01GM148075

Informations de copyright

© 2024. The Author(s).

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Auteurs

Aaron Franklin (A)

School of Biosciences, University of Birmingham, Birmingham, UK.

Vivian C Salgueiro (VC)

Department of Preventive Medicine, Public Health and Microbiology, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain.

Abigail J Layton (AJ)

School of Biosciences, University of Birmingham, Birmingham, UK.

Rudi Sullivan (R)

School of Biosciences, University of Birmingham, Birmingham, UK.

Todd Mize (T)

School of Biosciences, University of Birmingham, Birmingham, UK.

Lucía Vázquez-Iniesta (L)

Department of Preventive Medicine, Public Health and Microbiology, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain.

Samuel T Benedict (ST)

School of Biosciences, University of Birmingham, Birmingham, UK.

Sudagar S Gurcha (SS)

School of Biosciences, University of Birmingham, Birmingham, UK.

Itxaso Anso (I)

Structural Glycobiology Laboratory, Department of Structural and Molecular Biology, Molecular Biology Institute of Barcelona, Spanish National Research Council, Barcelona Science Park, c/Baldiri Reixac 10-12, Tower R, 08028, Barcelona, Catalonia, Spain.

Gurdyal S Besra (GS)

School of Biosciences, University of Birmingham, Birmingham, UK.

Manuel Banzhaf (M)

School of Biosciences, University of Birmingham, Birmingham, UK.

Andrew L Lovering (AL)

School of Biosciences, University of Birmingham, Birmingham, UK.

Spencer J Williams (SJ)

School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia.

Marcelo E Guerin (ME)

Structural Glycobiology Laboratory, Department of Structural and Molecular Biology; Molecular Biology Institute of Barcelona (IBMB), Spanish National Research Council (CSIC), Barcelona, Catalonia, Spain.

Nichollas E Scott (NE)

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

Rafael Prados-Rosales (R)

Department of Preventive Medicine, Public Health and Microbiology, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain.

Elisabeth C Lowe (EC)

Newcastle University Biosciences Institute, Medical School, Newcastle University, Newcastle upon Tyne, UK. elisabeth.lowe@ncl.ac.uk.

Patrick J Moynihan (PJ)

School of Biosciences, University of Birmingham, Birmingham, UK. p.j.moynihan@bham.ac.uk.

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