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

Author

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  • Aaron Franklin

    (University of Birmingham)

  • Vivian C. Salgueiro

    (Public Health and Microbiology, School of Medicine, Universidad Autonoma de Madrid)

  • Abigail J. Layton

    (University of Birmingham)

  • Rudi Sullivan

    (University of Birmingham)

  • Todd Mize

    (University of Birmingham)

  • Lucía Vázquez-Iniesta

    (Public Health and Microbiology, School of Medicine, Universidad Autonoma de Madrid)

  • Samuel T. Benedict

    (University of Birmingham)

  • Sudagar S. Gurcha

    (University of Birmingham)

  • Itxaso Anso

    (Spanish National Research Council)

  • Gurdyal S. Besra

    (University of Birmingham)

  • Manuel Banzhaf

    (University of Birmingham)

  • Andrew L. Lovering

    (University of Birmingham)

  • Spencer J. Williams

    (University of Melbourne)

  • Marcelo E. Guerin

    (Spanish National Research Council (CSIC))

  • Nichollas E. Scott

    (University of Melbourne at the Peter Doherty Institute for Infection and Immunity)

  • Rafael Prados-Rosales

    (Public Health and Microbiology, School of Medicine, Universidad Autonoma de Madrid)

  • Elisabeth C. Lowe

    (Newcastle University)

  • Patrick J. Moynihan

    (University of Birmingham)

Abstract

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.

Suggested Citation

  • Aaron Franklin & Vivian C. Salgueiro & Abigail J. Layton & Rudi Sullivan & Todd Mize & Lucía Vázquez-Iniesta & Samuel T. Benedict & Sudagar S. Gurcha & Itxaso Anso & Gurdyal S. Besra & Manuel Banzhaf , 2024. "The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50051-3
    DOI: 10.1038/s41467-024-50051-3
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    References listed on IDEAS

    as
    1. Sille Remm & Dario Vecchis & Jendrik Schöppe & Cedric A. J. Hutter & Imre Gonda & Michael Hohl & Simon Newstead & Lars V. Schäfer & Markus A. Seeger, 2023. "Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Ian L. Sparks & Takehiro Kado & Malavika Prithviraj & Japinder Nijjer & Jing Yan & Yasu S. Morita, 2024. "Lipoarabinomannan mediates localized cell wall integrity during division in mycobacteria," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Patrick J. Moynihan & Ian T. Cadby & Natacha Veerapen & Monika Jankute & Marialuisa Crosatti & Galina V. Mukamolova & Andrew L. Lovering & Gurdyal S. Besra, 2019. "The hydrolase LpqI primes mycobacterial peptidoglycan recycling," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    4. Fiona Cuskin & Elisabeth C. Lowe & Max J. Temple & Yanping Zhu & Elizabeth A. Cameron & Nicholas A. Pudlo & Nathan T. Porter & Karthik Urs & Andrew J. Thompson & Alan Cartmell & Artur Rogowski & Brian, 2015. "Correction: Corrigendum: Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism," Nature, Nature, vol. 520(7547), pages 388-388, April.
    5. Fiona Cuskin & Elisabeth C. Lowe & Max J. Temple & Yanping Zhu & Elizabeth A. Cameron & Nicholas A. Pudlo & Nathan T. Porter & Karthik Urs & Andrew J. Thompson & Alan Cartmell & Artur Rogowski & Brian, 2015. "Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism," Nature, Nature, vol. 517(7533), pages 165-169, January.
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