Intracellular Staphylococcus aureus persisters upon antibiotic exposure

Frédéric Peyrusson (1) , Hugo Varet (2) , Tiep Khac Nguyen (1) , Rachel Legendre (2) , Odile Sismeiro (3) , Jean-Yves Coppée (3) , Christiane Wolz (4) , Tanel Tenson (5) , Françoise van Bambeke (1)

1 Pharmacologie Cellulaire et Moléculaire [Brussels]
2 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
3 PF2 - Transcriptome et Epigénome
4 University of Tübingen
5 Institute of Technology [Tartu, Estonia]

Bacterial persister cells are phenotypic variants that exhibit a transient non-growing state and antibiotic tolerance. Here, we provide in vitro evidence of Staphylococcus aureus persisters within infected host cells. We show that the bacteria surviving antibiotic treatment within host cells are persisters, displaying biphasic killing and reaching a uniformly non-responsive, non-dividing state when followed at the single-cell level. This phenotype is stable but reversible upon antibiotic removal. Intracellular S. aureus persisters remain metabolically active but display an altered transcriptomic profile consistent with activation of stress responses, including the stringent response as well as cell wall stress, SOS and heat shock responses. These changes are associated with multidrug tolerance after exposure to a single antibiotic. We hypothesize that intracellular S. aureus persisters may constitute a reservoir for relapsing infection and could contribute to therapeutic failures.

Domains: Life Sciences [q-bio]; Bacteriology

Frédéric Peyrusson, Hugo Varet, Tiep Khac Nguyen, Rachel Legendre, Odile Sismeiro, et al.. Intracellular Staphylococcus aureus persisters upon antibiotic exposure. Nature Communications, 2020, 11 (1), ⟨10.1038/s41467-020-15966-7⟩. ⟨pasteur-02563041⟩