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

Dengler Haunreiter, Vanina; Tarnutzer, Andrea; Bär, Julian; von Matt, Manuela; Hertegonne, Sanne; Andreoni, Federica; Vulin, Clément; Künzi, Lisa; Menzi, Carmen; Kiefer, Patrick; Christen, Philipp; Vorholt, Julia A; Zinkernagel, Annelies S

doi:10.1128/spectrum.02788-23

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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, J. A., & Zinkernagel, A. S. (2023). C-di-AMP levels modulate Staphylococcus aureus cell wall thickness, response to oxidative stress, and antibiotic resistance and tolerance. Microbiology Spectrum, 11(6), e0278823. https://doi.org/10.1128/spectrum.02788-23

Abstract

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 resis