Mycobacterium tuberculosis modifies cell wall carbohydrates during biofilm growth with a concomitant reduction in complement activation

Thomas Keating, Samuel Lethbridge, Jon C. Allnutt, Charlotte L. Hendon-Dunn, Stephen R. Thomas, Luke J. Alderwick, Stephen C. Taylor, Joanna Bacon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

The development of new vaccines for TB needs to be underpinned by an understanding of both the molecular and cellular mechanisms of host-pathogen interactions and how the immune response can be modulated to achieve protection from disease. Complement orchestrates many aspects of the innate and adaptive immune responses. However, little is known about the contribution of the complement pathways during TB disease, particularly with respect to mycobacterial phenotype. Extracellular communities (biofilms) of M. tuberculosis are found in the acellular rim of granulomas, during disease, and these are likely to be present in post-primary TB episodes, in necrotic lesions. Our study aimed to determine which mycobacterial cell wall components were altered during biofilm growth and how these cell wall alterations modified the complement response. We have shown that M. tuberculosis biofilms modified their cell wall carbohydrates and elicited reduced classical and lectin pathway activation. Consistent with this finding was the reduction of C3b/iC3b deposition on biofilm cell wall carbohydrate extracts. Here, we have highlighted the role of cell wall carbohydrate alterations during biofilm growth of M. tuberculosis and subsequent modulation of complement activation.

Original languageEnglish
Article number100065
JournalCell Surface
Volume7
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
The work was funded by a Public Health England PhD studentship grant. The views expressed in this publication are those of the authors and not necessarily those of Public Health England or the Department of Health.

Publisher Copyright:
© 2021

Keywords

  • C1q
  • MBL
  • Mycobacterium tuberculosis
  • alpha glucan
  • biofilm
  • complement deposition

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