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 journalArticle

130 Citations (Scopus)

Abstract

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
Volume1
Issue number5
DOIs
StatePublished - Apr 18 2016

Fingerprint

Staphylococcus aureus
Adenosine Triphosphate
Anti-Bacterial Agents
Antitoxins
Infection
Gram-Positive Bacteria
Osteomyelitis
Endocarditis
Treatment Failure
Cell Count
Escherichia coli
Equipment and Supplies
Survival
Growth

ASJC Scopus subject areas

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

Cite this

Conlon, B. P., Rowe, S. E., Gandt, A. B., Nuxoll, A. S., Donegan, N. P., Zalis, E. A., ... Lewis, K. (2016). Persister formation in Staphylococcus aureus is associated with ATP depletion. Nature Microbiology, 1(5), [16051]. https://doi.org/10.1038/nmicrobiol.2016.51

Persister formation in Staphylococcus aureus is associated with ATP depletion. / Conlon, Brian P.; Rowe, Sarah E.; Gandt, Autumn Brown; Nuxoll, Austin S.; Donegan, Niles P.; Zalis, Eliza A.; Clair, Geremy; Adkins, Joshua N.; Cheung, Ambrose L.; Lewis, Kim.

In: Nature Microbiology, Vol. 1, No. 5, 16051, 18.04.2016.

Research output: Contribution to journalArticle

Conlon, BP, Rowe, SE, Gandt, AB, Nuxoll, AS, Donegan, NP, Zalis, EA, Clair, G, Adkins, JN, Cheung, AL & Lewis, K 2016, 'Persister formation in Staphylococcus aureus is associated with ATP depletion', Nature Microbiology, vol. 1, no. 5, 16051. https://doi.org/10.1038/nmicrobiol.2016.51
Conlon, Brian P. ; Rowe, Sarah E. ; Gandt, Autumn Brown ; Nuxoll, Austin S. ; Donegan, Niles P. ; Zalis, Eliza A. ; Clair, Geremy ; Adkins, Joshua N. ; Cheung, Ambrose L. ; Lewis, Kim. / Persister formation in Staphylococcus aureus is associated with ATP depletion. In: Nature Microbiology. 2016 ; Vol. 1, No. 5.
@article{5cf57816ae2d4ad79410d2e1386e8e05,
title = "Persister formation in Staphylococcus aureus is associated with ATP depletion",
abstract = "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.",
author = "Conlon, {Brian P.} and Rowe, {Sarah E.} and Gandt, {Autumn Brown} and Nuxoll, {Austin S.} and Donegan, {Niles P.} and Zalis, {Eliza A.} and Geremy Clair and Adkins, {Joshua N.} and Cheung, {Ambrose L.} and Kim Lewis",
year = "2016",
month = "4",
day = "18",
doi = "10.1038/nmicrobiol.2016.51",
language = "English (US)",
volume = "1",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Persister formation in Staphylococcus aureus is associated with ATP depletion

AU - Conlon, Brian P.

AU - Rowe, Sarah E.

AU - Gandt, Autumn Brown

AU - Nuxoll, Austin S.

AU - Donegan, Niles P.

AU - Zalis, Eliza A.

AU - Clair, Geremy

AU - Adkins, Joshua N.

AU - Cheung, Ambrose L.

AU - Lewis, Kim

PY - 2016/4/18

Y1 - 2016/4/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84978122872&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978122872&partnerID=8YFLogxK

U2 - 10.1038/nmicrobiol.2016.51

DO - 10.1038/nmicrobiol.2016.51

M3 - Article

C2 - 27572649

AN - SCOPUS:84978122872

VL - 1

JO - Nature Microbiology

JF - Nature Microbiology

SN - 2058-5276

IS - 5

M1 - 16051

ER -