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C-di-AMP levels modulate Staphylococcus aureus cell wall thickness, response to oxidative stress, and antibiotic

Vanina Dengler Haunreiter1, Andrea Tarnutzer1, Julian Bär1

  • 1Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich , Zurich, Switzerland.

Microbiology Spectrum
|November 10, 2023
PubMed
Abstract

Insights

High cyclic di-AMP levels in Staphylococcus aureus increase cell wall thickness, leading to greater resistance against antibiotics like oxacillin and fosfomycin. This finding is crucial for understanding antibiotic tolerance and resistance in clinical settings.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pharmacology

Background:

  • Antibiotic resistance and tolerance pose significant threats to public health.
  • Mutations in phosphodiesterase GdpP, affecting cyclic di-AMP (c-di-AMP) degradation, are linked to beta-lactam antibiotic resistance in *Staphylococcus aureus*.

Purpose of the Study:

  • To investigate the impact of high c-di-AMP levels on *S. aureus* cell morphology and antibiotic susceptibility.
  • To elucidate the role of c-di-AMP in the development of antibiotic resistance and tolerance.

Main Methods:

  • Generation of *S. aureus* mutant strains with altered c-di-AMP levels.
  • Microscopic analysis of bacterial cell size and cell wall thickness.
  • Assessment of antibiotic resistance and tolerance profiles using various antibiotics.

Main Results:

  • Elevated c-di-AMP levels resulted in decreased bacterial cell size and increased cell wall thickness.
  • Mutant strains exhibited enhanced resistance to cell wall-targeting antibiotics (oxacillin, fosfomycin).
  • Increased tolerance to ceftaroline, an antibiotic used for methicillin-resistant *S. aureus* (MRSA), was observed.

Conclusions:

  • c-di-AMP levels significantly influence *S. aureus* cell wall integrity and antibiotic response.
  • Targeting the c-di-AMP pathway could be a strategy to combat antibiotic resistance and tolerance.
  • Further research into c-di-AMP's role is vital for optimizing clinical antibiotic treatments.
Keywords:
Staphylococcus aureusantibiotic resistanceantibiotic tolerancec-di-AMPcell wall thicknessvirulence determinants

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