Persister formation in Staphylococcus aureus is associated with ATP depletion

Brian P. Conlon, Sarah E. Rowe, Autumn Brown Gandt, Austin S. Nuxoll, Niles P. Donegan, Eliza A. Zalis, Geremy Clair, Joshua N. Adkins, Ambrose L. Cheung, Kim Lewis

Research output: Contribution to journalArticlepeer-review

423 Scopus citations


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 languageEnglish (US)
Article number16051
JournalNature Microbiology
Issue number5
StatePublished - Apr 18 2016
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology


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