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Lookup NU author(s): Dr Elisabeth Lowe
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024.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.
Author(s): Franklin A, Salgueiro VC, Layton AJ, Sullivan R, Mize T, Vazquez-Iniesta L, Benedict ST, Gurcha SS, Anso I, Besra GS, Banzhaf M, Lovering AL, Williams SJ, Guerin ME, Scott NE, Prados-Rosales R, Lowe EC, Moynihan PJ
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2024
Volume: 15
Issue: 1
Online publication date: 09/07/2024
Acceptance date: 26/06/2024
Date deposited: 06/08/2024
ISSN (electronic): 2041-1723
Publisher: Nature Research
URL: https://doi.org/10.1038/s41467-024-50051-3
DOI: 10.1038/s41467-024-50051-3
Data Access Statement: The mass spectrometry proteomics data has been deposited in the Proteome Xchange Consortium via the PRIDE partner repository with the data set identifier PXD04265391. All data for the manuscript is provided either in the Supplementary Materials or in the Source Data file. Source data https://www.nature.com/articles/s41467-024-50051-3#Sec35 are provided with this paper.
PubMed id: 38982040
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