1. C-di-AMP levels modulate Staphylococcus aureus cell wall thickness, response to oxidative stress, and antibiotic resistance and tolerance.
- Author
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Dengler Haunreiter V, Tarnutzer A, Bär J, von Matt M, Hertegonne S, Andreoni F, Vulin C, Künzi L, Menzi C, Kiefer P, Christen P, Vorholt JA, and Zinkernagel AS
- 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
- 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., Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
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