A dysfunctional tricarboxylic acid cycle enhances fitness of Staphylococcus epidermidis during β-lactam stress

Vinai Chittezham Thomas, Lauren C. Kinkead, Ashley Janssen, Carolyn R. Schaeffer, Keith M. Woods, Jill K. Lindgren, Jonathan M. Peaster, Sujata S. Chaudhari, Marat Sadykov, Joselyn Jones, Sameh M. Mohamadi AbdelGhani, Matthew C Zimmerman, Kenneth W Bayles, Greg A Somerville, Paul D Fey

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these antibiotics. The increased protection from β-lactam antibiotics could result from pleiotropic effects of a dysfunctional TCA cycle, including increased resistance to oxidative stress, reduced susceptibility to autolysis, and a more positively charged cell surface. IMPORTANCE Staphylococcus epidermidis, a normal inhabitant of the human skin microflora, is the most common cause of indwelling medical device infections. In the present study, we analyzed 126 clinical S. epidermidis isolates and discovered that tricarboxylic acid (TCA) cycle dysfunctions are relatively common in the clinical environment. We determined that a dysfunctional TCA cycle enables S. epidermidis to resist oxidative stress and alter its cell surface properties, making it less susceptible to β-lactam antibiotics.

Original languageEnglish (US)
JournalmBio
Volume4
Issue number4
DOIs
StatePublished - Aug 20 2013

Fingerprint

Lactams
Citric Acid Cycle
Staphylococcus epidermidis
Anti-Bacterial Agents
Reactive Oxygen Species
Oxidative Stress
Tricarboxylic Acids
Autolysis
Oxacillin
Surface Properties
Cell Death
Equipment and Supplies
Skin
Infection

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

A dysfunctional tricarboxylic acid cycle enhances fitness of Staphylococcus epidermidis during β-lactam stress. / Chittezham Thomas, Vinai; Kinkead, Lauren C.; Janssen, Ashley; Schaeffer, Carolyn R.; Woods, Keith M.; Lindgren, Jill K.; Peaster, Jonathan M.; Chaudhari, Sujata S.; Sadykov, Marat; Jones, Joselyn; Mohamadi AbdelGhani, Sameh M.; Zimmerman, Matthew C; Bayles, Kenneth W; Somerville, Greg A; Fey, Paul D.

In: mBio, Vol. 4, No. 4, 20.08.2013.

Research output: Contribution to journalArticle

Chittezham Thomas, V, Kinkead, LC, Janssen, A, Schaeffer, CR, Woods, KM, Lindgren, JK, Peaster, JM, Chaudhari, SS, Sadykov, M, Jones, J, Mohamadi AbdelGhani, SM, Zimmerman, MC, Bayles, KW, Somerville, GA & Fey, PD 2013, 'A dysfunctional tricarboxylic acid cycle enhances fitness of Staphylococcus epidermidis during β-lactam stress', mBio, vol. 4, no. 4. https://doi.org/10.1128/mBio.00437-13
Chittezham Thomas, Vinai ; Kinkead, Lauren C. ; Janssen, Ashley ; Schaeffer, Carolyn R. ; Woods, Keith M. ; Lindgren, Jill K. ; Peaster, Jonathan M. ; Chaudhari, Sujata S. ; Sadykov, Marat ; Jones, Joselyn ; Mohamadi AbdelGhani, Sameh M. ; Zimmerman, Matthew C ; Bayles, Kenneth W ; Somerville, Greg A ; Fey, Paul D. / A dysfunctional tricarboxylic acid cycle enhances fitness of Staphylococcus epidermidis during β-lactam stress. In: mBio. 2013 ; Vol. 4, No. 4.
@article{cb2848904a664355bcbb5d3c45f640f9,
title = "A dysfunctional tricarboxylic acid cycle enhances fitness of Staphylococcus epidermidis during β-lactam stress",
abstract = "A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these antibiotics. The increased protection from β-lactam antibiotics could result from pleiotropic effects of a dysfunctional TCA cycle, including increased resistance to oxidative stress, reduced susceptibility to autolysis, and a more positively charged cell surface. IMPORTANCE Staphylococcus epidermidis, a normal inhabitant of the human skin microflora, is the most common cause of indwelling medical device infections. In the present study, we analyzed 126 clinical S. epidermidis isolates and discovered that tricarboxylic acid (TCA) cycle dysfunctions are relatively common in the clinical environment. We determined that a dysfunctional TCA cycle enables S. epidermidis to resist oxidative stress and alter its cell surface properties, making it less susceptible to β-lactam antibiotics.",
author = "{Chittezham Thomas}, Vinai and Kinkead, {Lauren C.} and Ashley Janssen and Schaeffer, {Carolyn R.} and Woods, {Keith M.} and Lindgren, {Jill K.} and Peaster, {Jonathan M.} and Chaudhari, {Sujata S.} and Marat Sadykov and Joselyn Jones and {Mohamadi AbdelGhani}, {Sameh M.} and Zimmerman, {Matthew C} and Bayles, {Kenneth W} and Somerville, {Greg A} and Fey, {Paul D}",
year = "2013",
month = "8",
day = "20",
doi = "10.1128/mBio.00437-13",
language = "English (US)",
volume = "4",
journal = "mBio",
issn = "2161-2129",
publisher = "American Society for Microbiology",
number = "4",

}

TY - JOUR

T1 - A dysfunctional tricarboxylic acid cycle enhances fitness of Staphylococcus epidermidis during β-lactam stress

AU - Chittezham Thomas, Vinai

AU - Kinkead, Lauren C.

AU - Janssen, Ashley

AU - Schaeffer, Carolyn R.

AU - Woods, Keith M.

AU - Lindgren, Jill K.

AU - Peaster, Jonathan M.

AU - Chaudhari, Sujata S.

AU - Sadykov, Marat

AU - Jones, Joselyn

AU - Mohamadi AbdelGhani, Sameh M.

AU - Zimmerman, Matthew C

AU - Bayles, Kenneth W

AU - Somerville, Greg A

AU - Fey, Paul D

PY - 2013/8/20

Y1 - 2013/8/20

N2 - A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these antibiotics. The increased protection from β-lactam antibiotics could result from pleiotropic effects of a dysfunctional TCA cycle, including increased resistance to oxidative stress, reduced susceptibility to autolysis, and a more positively charged cell surface. IMPORTANCE Staphylococcus epidermidis, a normal inhabitant of the human skin microflora, is the most common cause of indwelling medical device infections. In the present study, we analyzed 126 clinical S. epidermidis isolates and discovered that tricarboxylic acid (TCA) cycle dysfunctions are relatively common in the clinical environment. We determined that a dysfunctional TCA cycle enables S. epidermidis to resist oxidative stress and alter its cell surface properties, making it less susceptible to β-lactam antibiotics.

AB - A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these antibiotics. The increased protection from β-lactam antibiotics could result from pleiotropic effects of a dysfunctional TCA cycle, including increased resistance to oxidative stress, reduced susceptibility to autolysis, and a more positively charged cell surface. IMPORTANCE Staphylococcus epidermidis, a normal inhabitant of the human skin microflora, is the most common cause of indwelling medical device infections. In the present study, we analyzed 126 clinical S. epidermidis isolates and discovered that tricarboxylic acid (TCA) cycle dysfunctions are relatively common in the clinical environment. We determined that a dysfunctional TCA cycle enables S. epidermidis to resist oxidative stress and alter its cell surface properties, making it less susceptible to β-lactam antibiotics.

UR - http://www.scopus.com/inward/record.url?scp=84883310846&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883310846&partnerID=8YFLogxK

U2 - 10.1128/mBio.00437-13

DO - 10.1128/mBio.00437-13

M3 - Article

VL - 4

JO - mBio

JF - mBio

SN - 2161-2129

IS - 4

ER -