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C-di-AMP levels modulate Staphylococcus aureus cell wall thickness, response to oxidative stress, and antibiotic resistance and tolerance.
C-di-AMP levels modulate Staphylococcus aureus cell wall thickness, response to oxidative stress, and antibiotic resistance and tolerance.
- Source :
-
Microbiology spectrum [Microbiol Spectr] 2023 Dec 12; Vol. 11 (6), pp. e0278823. Date of Electronic Publication: 2023 Nov 10. - Publication Year :
- 2023
-
Abstract
- Importance: Antibiotic resistance and tolerance are substantial healthcare-related problems, hampering effective treatment of bacterial infections. Mutations in the phosphodiesterase GdpP, which degrades cyclic di-3', 5'-adenosine monophosphate (c-di-AMP), have recently been associated with resistance to beta-lactam antibiotics in clinical Staphylococcus aureus isolates. In this study, we show that high c-di-AMP levels decreased the cell size and increased the cell wall thickness in S. aureus mutant strains. As a consequence, an increase in resistance to cell wall targeting antibiotics, such as oxacillin and fosfomycin as well as in tolerance to ceftaroline, a cephalosporine used to treat methicillin-resistant S. aureus infections, was observed. These findings underline the importance of investigating the role of c-di-AMP in the development of tolerance and resistance to antibiotics in order to optimize treatment in the clinical setting.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- Humans
Staphylococcus aureus metabolism
Anti-Bacterial Agents pharmacology
Anti-Bacterial Agents metabolism
Cell Wall metabolism
Methicillin Resistance
Oxidative Stress
Bacterial Proteins genetics
Microbial Sensitivity Tests
Methicillin-Resistant Staphylococcus aureus genetics
Staphylococcal Infections drug therapy
Staphylococcal Infections metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2165-0497
- Volume :
- 11
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Microbiology spectrum
- Publication Type :
- Academic Journal
- Accession number :
- 37948390
- Full Text :
- https://doi.org/10.1128/spectrum.02788-23