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  3. Staphylococcus Aureus Cell Wall Structure And Dynamics During Host-pathogen Interaction.
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  3. Staphylococcus Aureus Cell Wall Structure And Dynamics During Host-pathogen Interaction.

Related Experiment Video

Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
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Staphylococcus aureus cell wall structure and dynamics during host-pathogen interaction.

Joshua A F Sutton1,2, Oliver T Carnell1,2, Lucia Lafage1,2

  • 1Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, United Kingdom.

Plos Pathogens
|March 31, 2021

View abstract on PubMed

Summary
This summary is machine-generated.

Staphylococcus aureus cell wall structure changes during infection, impacting antibiotic effectiveness. Key enzymes like PBP4 and SagB are crucial for virulence, offering new therapeutic targets.

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Area of Science:

  • Microbiology
  • Infectious Diseases
  • Biochemistry

Background:

  • Peptidoglycan is vital for Staphylococcus aureus cell wall integrity and antibiotic targeting.
  • Understanding peptidoglycan dynamics during infection is crucial but poorly understood.

Purpose of the Study:

  • To investigate Staphylococcus aureus cell wall structure and dynamics during active infection ex vivo.
  • To determine the role of peptidoglycan homeostatic mechanisms, specifically PBP4 and glucosaminidases, in pathogenesis.

Main Methods:

  • Developed methods to harvest bacteria from active infections for ex vivo cell wall analysis.
  • Utilized genetic manipulation of Staphylococcus aureus (e.g., PBP4, SagB knockouts) and infection models (mice, zebrafish, macrophages).

Main Results:

  • Ex vivo bacterial cells exhibit smaller size, thickened cell walls, and reduced peptidoglycan crosslinking compared to in vitro growth.
  • Loss of PBP4 increased S. aureus recovery from mouse livers and enhanced survival in macrophages.
  • Deficiency in SagB attenuated virulence in mice and reduced survival in human macrophages.
  • Loss of Atl, SagA, and ScaH caused clustering-dependent attenuation in zebrafish embryos.

Conclusions:

  • Appropriate cell wall structure and dynamics are critical for Staphylococcus aureus pathogenesis.
  • PBP4 and SagB play significant roles in S. aureus virulence, representing potential therapeutic targets.