Persisters are dormant phenotypic variants of bacterial cells that are tolerant to killing by antibiotics 1. Persisters are associated with chronic infections and antibiotic treatment failure 1-3. In Escherichia coli, toxin-antitoxin modules have been linked to persister formation 4-6. The mechanism of persister formation in Gram-positive bacteria is unknown. Staphylococcus aureus is a major human pathogen, responsible for a variety of chronic and relapsing infections such as osteomyelitis, endocarditis and infections of implanted devices. Deleting toxin-antitoxin modules in S. aureus did not affect the level of persisters. Here, we show that S. aureus persisters are produced due to a stochastic entrance into the stationary phase accompanied by a drop in intracellular adenosine triphosphate. Cells expressing stationary-state markers are present throughout the growth phase, and increase in frequency with cell density. Cell sorting revealed that the expression of stationary markers is associated with a 100-1,000-fold increase in the likelihood of survival to antibiotic challenge. The adenosine triphosphate level of the cell is predictive of bactericidal antibiotic efficacy and explains bacterial tolerance to antibiotics.
|Original language||English (US)|
|State||Published - Apr 18 2016|
ASJC Scopus subject areas
- Applied Microbiology and Biotechnology
- Microbiology (medical)
- Cell Biology