Persister formation in Staphylococcus aureus is associated with ATP depletion.
Brian P ConlonSarah E RoweAutumn Brown GandtAustin S NuxollNiles P DoneganEliza A ZalisGeremy ClairJoshua N AdkinsAmbrose L CheungKim LewisPublished in: Nature microbiology (2016)
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.
Keyphrases
- escherichia coli
- staphylococcus aureus
- single cell
- induced apoptosis
- cell therapy
- multiple sclerosis
- cell cycle arrest
- endothelial cells
- poor prognosis
- biofilm formation
- liquid chromatography
- mesenchymal stem cells
- oxidative stress
- mass spectrometry
- cell proliferation
- cystic fibrosis
- systemic lupus erythematosus
- dna methylation
- cell death
- gram negative
- induced pluripotent stem cells
- disease activity
- bone marrow
- reactive oxygen species
- smoking cessation
- candida albicans
- methicillin resistant staphylococcus aureus