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

Autor: Franklin A; School of Biosciences, University of Birmingham, Birmingham, UK., Salgueiro VC; Department of Preventive Medicine, Public Health and Microbiology, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain., Layton AJ; School of Biosciences, University of Birmingham, Birmingham, UK., Sullivan R; School of Biosciences, University of Birmingham, Birmingham, UK., Mize T; School of Biosciences, University of Birmingham, Birmingham, UK., Vázquez-Iniesta L; Department of Preventive Medicine, Public Health and Microbiology, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain., Benedict ST; School of Biosciences, University of Birmingham, Birmingham, UK., Gurcha SS; School of Biosciences, University of Birmingham, Birmingham, UK., 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., Besra GS; School of Biosciences, University of Birmingham, Birmingham, UK., Banzhaf M; School of Biosciences, University of Birmingham, Birmingham, UK., Lovering AL; School of Biosciences, University of Birmingham, Birmingham, UK., Williams SJ; School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia., 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., Scott NE; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Prados-Rosales R; Department of Preventive Medicine, Public Health and Microbiology, School of Medicine, Universidad Autonoma de Madrid, Madrid, Spain., Lowe EC; Newcastle University Biosciences Institute, Medical School, Newcastle University, Newcastle upon Tyne, UK. elisabeth.lowe@ncl.ac.uk., Moynihan PJ; School of Biosciences, University of Birmingham, Birmingham, UK. p.j.moynihan@bham.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 09; Vol. 15 (1), pp. 5740. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1038/s41467-024-50051-3
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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