1. Nat Commun. 2020 May 4;11(1):2200. doi: 10.1038/s41467-020-15966-7.

Intracellular Staphylococcus aureus persisters upon antibiotic exposure.

Peyrusson F(1), Varet H(2), Nguyen TK(1), Legendre R(2), Sismeiro O(3), Coppée 
JY(3), Wolz C(4), Tenson T(5), Van Bambeke F(6).

Author information:
(1)Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, 
Université catholique de Louvain (UCLouvain), Brussels, Belgium.
(2)Hub de Bioinformatique et Biostatistique - Département Biologie 
Computationnelle, Institut Pasteur, USR 3756 CNRS, Paris, France.
(3)Institut Pasteur, Plate-forme Transcriptome et Epigenome, Biomics, Centre de 
Ressources et Recherches Technologiques (C2RT), Paris, France.
(4)Institut für Medizinische Mikrobiologie und Hygiene, Tübingen, Germany.
(5)Institute of Technology, University of Tartu, Tartu, Estonia.
(6)Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, 
Université catholique de Louvain (UCLouvain), Brussels, Belgium. 
francoise.vanbambeke@uclouvain.be.

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.

DOI: 10.1038/s41467-020-15966-7
PMCID: PMC7198484
PMID: 32366839 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.