Persister formation in Staphylococcus aureus is associated with ATP depletion
Persisters are dormant phenotypic variants of bacterial cells that are tolerant to killing by antibiotics1. Persisters are associated with chronic bacterial infection and antibiotic treatment failure. In Escherichia coli, toxin/antitoxin (TA) modules are responsible for persister formation. 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 TA 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 to stationary phase accompanied by a drop in intracellular ATP. Cells expressing stationary state markers are present throughout the growth phase, increasing in frequency with cell density. Cell sorting revealed that expression of stationary markers was associated with a 100-1000 fold increased likelihood of survival to antibiotic challenge. We find that the antibiotic tolerance of these cells is due to a drop in intracellular ATP. The ATP level of the cell is predictive of bactericidal antibiotic efficacy and explains bacterial tolerance to antibiotic treatment.
- Research Organization:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 1333435
- Report Number(s):
- PNNL-SA-116412; 453040220
- Journal Information:
- Nature Microbiology, Journal Name: Nature Microbiology Journal Issue: 5 Vol. 1; ISSN 2058-5276
- Country of Publication:
- United States
- Language:
- English
Similar Records
Stochastic Variation in Expression of the Tricarboxylic Acid Cycle Produces Persister Cells
CHI3L1 promotes Staphylococcus aureus-induced osteomyelitis by activating p38/MAPK and Smad signaling pathways