Competition with Pseudomonas aeruginosa induces Staphylococcus aureus in an antibiotic-tolerant viable but non culturable state

Interactions between different species of pathogenic microbes often affect clinical outcome by altering the virulence or antibiotic resistance of individual microbes. By investigating the interactions between Staphylococcus aureus and Pseudomonas aeruginosa at the population, single-cell and molecular level we discovered that a sub-population of S. aureus enters in a viable non-culturable state that it is not detected via standard microbiology assays. In the presence of P. aeruginosa, S. aureus adopts a survival lifestyle similar to previously described intracellular S. aureus persisters, downregulating nitrogen metabolism and amino acid biosynthesis, while upregulating protein maturation processes. Entrance in a viable but non culturable state is the primary survival strategy of S. aureus in response to vancomycin treatment, whereas only a minority of the S. aureus population survive ciprofloxacin treatment while in a viable but non culturable state. These bacterial interactions may shape the evolution of resistance traits of co-infecting pathogens. Manipulating these interspecies adaptations could provide new opportunities for early therapeutic interventions.