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

Autor:	Dengler Haunreiter V; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich , Zurich, Switzerland., Tarnutzer A; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich , Zurich, Switzerland., Bär J; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich , Zurich, Switzerland., von Matt M; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich , Zurich, Switzerland., Hertegonne S; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich , Zurich, Switzerland., Andreoni F; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich , Zurich, Switzerland., Vulin C; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich , Zurich, Switzerland., Künzi L; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich , Zurich, Switzerland., Menzi C; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich , Zurich, Switzerland., Kiefer P; Department of Biology, Institute of Microbiology, ETH Zurich , Zurich, Switzerland., Christen P; Department of Biology, Institute of Microbiology, ETH Zurich , Zurich, Switzerland., Vorholt JA; Department of Biology, Institute of Microbiology, ETH Zurich , Zurich, Switzerland., Zinkernagel AS; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich , Zurich, Switzerland.
Jazyk:	angličtina
Zdroj:	Microbiology spectrum [Microbiol Spectr] 2023 Dec 12; Vol. 11 (6), pp. e0278823. Date of Electronic Publication: 2023 Nov 10.
DOI:	10.1128/spectrum.02788-23
Abstrakt:	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.
Databáze:	MEDLINE
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