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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.

Authors :
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
Zinkernagel AS
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.

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