Understanding the role of D-arabinanases in mycobacterial physiology and pathogenicity

Year of award: 2023

Grantholders

  • Dr Elisabeth Lowe

    Newcastle University, United Kingdom

  • Dr Serge Mostowy

    London School of Hygiene & Tropical Medicine, United Kingdom

  • Prof Spencer Williams

    University of Melbourne, Australia

  • Prof Tracy Palmer

    Newcastle University, United Kingdom

  • Dr Patrick Moynihan

    University of Birmingham, United Kingdom

Project summary

The mycobacterial cell envelope is a complex structure critical for interactions with the host and other bacteria. An important class of cell wall molecules are the D-arabinan containing polysaccharides arabinogalactan and lipoarabinomannan. Decades of research has focused on the biosynthesis of these molecules, with little understanding of how bacteria modify or degrade these structures post-synthesis.

We recently discovered a new family of enzymes with endo-D-arabinanase activity and we provide evidence that these enzymes fall into three functional classes:

- cell maintenance

- inter-bacterial competition

- immune modulation.

The diversity of functions ascribed to these enzymes underscores the importance of their activity to mycobacterial biology, and yet we know almost nothing about their specificity, how they are regulated, how they contribute to cell fitness or how they enable survival in the host.

Our research team has been assembled to draw on crucial expertise to address these questions using cutting-edge approaches and technologies. Together, this research programme will provide a transformative view of mycobacterial cell surface variation, and revolutionise our understanding of mycobacterial interactions with other bacteria and host cells. It could also lead to new diagnostics, therapeutics or vaccines against mycobacterial diseases such as tuberculosis.