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PreprintCited by 0Antimicrobial Resistance in StaphylococcusBacterial Genetics and BiotechnologyStreptococcal Infections and Treatments

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Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia

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Douglas, Edward J.A., Palk, Nathanael, Brignoli, Tarcisio, Altwiley, Dina, Boura, Marcia, Laabei, Maisem, Recker, Mario, Cheung, Gordon Y.C., Liu, Ryan, Hsieh, Roger C., Otto, Michael, O’Brien, Eoin, McLoughlin, Rachel M., Massey, Ruth C.·2023·bioRxiv (Cold Spring Harbor Laboratory)
DOI 10.1101/2023.02.23.529713PMC PMC9980097

Preprint — published as 10.7554/elife.87026.3 · Paper page

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Abstract

Introductory Paragraph / 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.

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Metadata

Authors
Douglas, E. J. A., Palk, N., Brignoli, T., Altwiley, D., Boura, M., Laabei, M., Recker, M., Cheung, G. Y. C., Liu, R., Hsieh, R. C., Otto, M., O’Brien, E., McLoughlin, R. M., & Massey, R. C.
Affiliations
  • University of Bristol (GB)
  • University of Milan (IT)
  • University of Bath (GB)
  • University of Exeter (GB)
  • National Institutes of Health (US)
  • Trinity College Dublin (IE)
  • University College Cork (IE)
Corresponding author
Massey, Ruth C.
ORCID
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2023-02-23
DOI
10.1101/2023.02.23.529713
PMC
PMC9980097
OpenAlex
W4321604849
Cited by
0
References
1
Type
posted content
Language
en
Open access
Licence
cc-by
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • Wellcome Trust (212258/Z/18/Z, 202846/Z/16/Z, 212258, 202846)
  • Saudi Arabian Cultural Bureau
  • Academy of Medical Sciences (SBF006, (SBF006/1023))
  • University of Bristol
  • National Institutes of Health (AI000904)
  • Biotechnology and Biological Sciences Research Council
  • National Institute of Allergy and Infectious Diseases (AI000904, ZIAAI000904)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Infectious Diseases › Streptococcal Infections and Treatments
Keywords
Staphylococcus aureus, bacteremia, wall teichoic acid, cell wall remodeling, serum resistance, virulence factors, peptidoglycan cross-linking, antimicrobial peptides, antibiotic susceptibility, autolysis, mouse infection model

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