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

Lookup NU author(s): Dr Elisabeth Lowe

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Abstract

© 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.

Publication metadata

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

ISSN (electronic): 2041-1723

Publisher: Nature Research

URL: https://doi.org/10.1038/s41467-024-50051-3

DOI: 10.1038/s41467-024-50051-3

PubMed id: 38982040

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