Year: 2023
Type: article
Abstract: Bacterial cell growth and division require the coordinated action of enzymes that synthesize and degrade cell wall polymers. Here, we identify enzymes that cleave the d -arabinan core of arabinogalactan, an unusual component of the cell wall of Mycobacterium tuberculosis and other mycobacteria. We screened 14 human gut-derived Bacteroidetes for arabinogalactan-degrading activities and identified four families of glycoside hydrolases with activity against the d -arabinan or d -galactan components of arabinogalactan. Using one of these isolates with exo- d -galactofuranosidase activity, we generated enriched d -arabinan and used it to identify a strain of Dysgonomonas gadei as a d -arabinan degrader. This enabled the discovery of endo- and exo-acting enzymes that cleave d -arabinan, including members of the DUF2961 family (GH172) and a family of glycoside hydrolases (DUF4185/GH183) that display endo- d -arabinofuranase activity and are conserved in mycobacteria and other microbes. Mycobacterial genomes encode two conserved endo- d -arabinanases with different preferences for the d -arabinan-containing cell wall components arabinogalactan and lipoarabinomannan, suggesting they are important for cell wall modification and/or degradation. The discovery of these enzymes will support future studies into the structure and function of the mycobacterial cell wall.
Source: Nature Communications
Authors: Omar Al-Jourani, Samuel T. Benedict, Jennifer Ross, Abigail J. Layton, Phillip van der Peet, Victoria M. Marando, Nicholas P. Bailey, Tiaan Heunis, Joseph Manion, Francesca Mensitieri, Aaron Franklin, Javier Abellon-Ruiz, Sophia L. Oram, Lauren Parsons, Alan Cartmell, Gareth S. A. Wright, Arnaud Baslé, Matthias Trost, Bernard Henrissat, Jose Munoz-Munoz, Robert P. Hirt, Laura L. Kiessling, Andrew L. Lovering, Spencer J. Williams, Elisabeth C. Lowe, Patrick J. Moynihan
Institutions: Newcastle University, University of Birmingham, The University of Melbourne, Broad Institute, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology, University of Liverpool, University of Essex, King Abdulaziz University, Technical University of Denmark, Northumbria University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: Wellcome Trust, Royal Society, Academy of Medical Sciences, Novo Nordisk Fonden, National Institutes of Health, Directorate for Biological Sciences, Biotechnology and Biological Sciences Research Council, Australian Research Council, National Institute of General Medical Sciences, FP7 Ideas: European Research Council, Common Fund
Awards: G1047747990, Dissecting a major sulfur cycling pathway: sulfoglycolysis, Supporting EI’s ISPs and the UK Community with Genomics and Single Cell Analysis, The Effect of β2-agonists on the Suppressive Effect of Corticosteroids in Airway Smooth Muscle Cells in Asthma, Combating Gram Negative AMR Pathogens by Understanding the Envelope-Breaching Mechanisms of Predatory Bacteria, Understanding and exploiting complex glycan metabolism in the human microbiota, G339059223, G3659614836, G3803651186, G399966401, G4573353522, G4880922690, Combating Gram Negative AMR Pathogens by Understanding the Envelope-Breaching Mechanisms of Predatory Bacteria, G5728235598, Newcastle Liverpool Durham BBSRC DTP2, Chemoenzymatic synthesis of bacterial polysaccharides, Peptidoglycan release and recycling in pathogenic mycobacteria., G7176628207, G7483351365, BBSRC National Bioscience Research Infrastructure: Transformative Genomics, G812075936
OpenAlex ID: W4366405454