Intracellular Staphylococcus aureus persisters upon antibiotic exposure

Area of Science:

• Microbiology
• Infectious Diseases
• Bacterial Pathogenesis

Background:

• Bacterial persister cells are phenotypic variants known for their transient non-growing state and antibiotic tolerance.
• Staphylococcus aureus is a significant human pathogen often associated with persistent and recurrent infections.

Purpose of the Study:

• To provide in vitro evidence of Staphylococcus aureus persisters within host cells.
• To characterize the phenotype and transcriptomic profile of intracellular S. aureus persisters.

Main Methods:

• In vitro infection models using host cells.
• Single-cell level analysis of bacterial survival and behavior.
• Transcriptomic profiling (RNA sequencing) of intracellular bacteria.

Main Results:

• Evidence of Staphylococcus aureus persisters within host cells was demonstrated.
• Intracellular persisters exhibited biphasic killing, a non-responsive, non-dividing state, and stable but reversible phenotype.
• Metabolically active intracellular persisters showed altered transcriptomic profiles indicative of stress responses (stringent, cell wall, SOS, heat shock).
• These stress responses correlated with multidrug tolerance.

Conclusions:

• Intracellular Staphylococcus aureus persisters are identified within host cells.
• These persisters possess a unique transcriptomic signature linked to stress responses and multidrug tolerance.
• Intracellular persisters may serve as a reservoir for recurrent infections and contribute to antibiotic treatment failures.