Persister formation in Staphylococcus aureus is associated with ATP depletion

By Brian P. Conlon, Sarah E. Rowe, Autumn Brown Gandt, Austin S. Nuxoll, N. Donegan, Eliza A. Zalis, G. Clair, J. Adkins, A. Cheung, Kim Lewis. Nature Microbiology, 2016

595 citations recorded by the source corpus.

Persisters are dormant phenotypic variants of bacterial cells that are tolerant to killing by antibiotics1. Persisters are associated with chronic infections and antibiotic treatment failure1–3. In Escherichia coli, toxin–antitoxin modules have been linked to persister formation4–6. 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.

Subfields: Genetics, Infectious Diseases, Molecular Medicine

View Paper: https://www.semanticscholar.org/paper/e4ae54a1ebdfd077054faa30c11419a8032c8687

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Kenn Gerdes
2. T. Foster
3. Etienne Maisonneuve
4. Alexander Harms
5. B. Bassler
6. Brian K. Hammer

In Infectious Diseases

1. Jing Yan
2. T. Foster
3. B. Bassler

In Molecular Medicine

1. Kenn Gerdes
2. T. Foster
3. Etienne Maisonneuve
4. Alexander Harms
5. B. Bassler

Citations in the corpus

• Antibiotic resistance in Staphylococcus aureus. Current status and future prospects (2017, background): “aureus, the mechanism controlling entry into the persister state is completely different to that of Gram-negative bacteria (Conlon et al. 2016).”
• Antibiotic resistance and persistence—Implications for human health and treatment perspectives (2020, unknown): “A drop in ATP levels has been associated with antibiotic tolerance in E. coli (Shan et al , 2017) and S. aureu s (Conlon et al , 2016).”
• Mechanisms of bacterial persistence during stress and antibiotic exposure (2016, background): “Like TisB, HokB is a membrane-targeted type I toxin that disrupts the proton-motive force to impair ATP synthesis and induce dormancy (Fig.”
• Surviving as a community: antibiotic tolerance and persistence in bacterial biofilms (2019, background): “TA modules do not appear to underlie persistence in Staphylococcus aureus as elimination of all TAs had no effect on persister cell formation (Conlon et al., 2016).”