Intracellular Staphylococcus aureus persisters upon antibiotic exposure

Frédéric Peyrusson, Hugo Varet, Tiep Khac Nguyen, Rachel Legendre, Odile Sismeiro, Jean-Yves Coppée, Christiane Wolz, Tanel Tenson and Françoise Van Bambeke ()
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Frédéric Peyrusson: Université catholique de Louvain (UCLouvain)
Hugo Varet: Institut Pasteur, USR 3756 CNRS
Tiep Khac Nguyen: Université catholique de Louvain (UCLouvain)
Rachel Legendre: Institut Pasteur, USR 3756 CNRS
Odile Sismeiro: Centre de Ressources et Recherches Technologiques (C2RT)
Jean-Yves Coppée: Centre de Ressources et Recherches Technologiques (C2RT)
Christiane Wolz: Institut für Medizinische Mikrobiologie und Hygiene
Tanel Tenson: University of Tartu
Françoise Van Bambeke: Université catholique de Louvain (UCLouvain)

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-15966-7

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