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Persister cells, a tolerant cell sub-population, are commonly associated with chronic and recurrent infections. However, little is known about their ability to actually initiate or establish an infection, become virulent and cause pathogenicity within a host. Here we investigated whether  Staphylococcus aureus  persister cells initiate an infection and are recognized by macrophages, while in a persister cell status, and upon awakening due to exposure to  cis -2-decenoic acid ( cis -DA). Our results show that  S. aureus  persister cells are not able to initiate infections in  A. thaliana  and present significantly reduced virulence towards  C. elegans  compared to total populations. In contrast, awakened  S. aureus  persister cells are able to initiate infections in  A. thaliana  and in  C. elegans  albeit, with lower mortality than total population. Furthermore, exposure of  S. aureus  persister cells to  cis -DA led to a loss of tolerance to ciprofloxacin, and an increase of the bacterial fluorescence to levels found in total population. In addition, macrophage engulfment of persister cells was significantly lower than engulfment of total population, both before and following awakening. Overall our findings indicate that upon awakening of a persister population the cells regain their ability to infect hosts despite the absence of an increased immune response.

Interaction of Staphylococcus aureus persister cells with the host when in a persister state and following awakening