Extensive remodelling of the cell wall during the development of Staphylococcus aureus bacteraemia

Edward J.A. Douglas, Nathanael Palk, Tarcisio Brignoli, Dina Altwiley, Marcia Boura, Maisem Laabei, Mario Recker, Gordon C.Y. Cheung, Ryan Liu, Roger C. Hseih, Michael Otto, Eoin O'Brien, Rachel M. McLoughlin, Ruth C. Massey

Research output: Contribution to journalArticlepeer-review

2 Citations (SciVal)

Abstract

The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.

Original languageEnglish
JournaleLife
Volume12
Early online date4 Jul 2023
DOIs
Publication statusE-pub ahead of print - 4 Jul 2023

Bibliographical note

Funding information:
EJAD was funded on a studentship provided by the School of Cellular and Molecular medicine, University of Bristol.
NP is funded on a BBSRC SWBio DTOP PhD Studentship.
DA is funded by a PhD studentship awarded by the Saudi Arabian Cultural Bureau. RCMs and RMM are both Wellcome Trust Investigators (Grant reference numbers: 212258/Z/18/Z and 202846/Z/16/Z).
MO is supported by the Intramural Research Program of the National Institutes of Allergic and Infectious Diseases (NIAID), US National Institutes of Health (NIH), project number ZIA AI000904.
ML acknowledges funding from the Academy of Medical Sciences (SBF006\1023).

Keywords

  • bacteraemia
  • infectious disease
  • microbiology
  • staphylococcus aureus
  • Staphylococcus aureus
  • TcaA

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology

Fingerprint

Dive into the research topics of 'Extensive remodelling of the cell wall during the development of Staphylococcus aureus bacteraemia'. Together they form a unique fingerprint.

Cite this