A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness of <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> 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 oxaci...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0e957108156f4ea585a2b4484c5cb040
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spelling	oai:doaj.org-article:0e957108156f4ea585a2b4484c5cb0402021-11-15T15:43:09ZA Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness of <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> During β-Lactam Stress10.1128/mBio.00437-132150-7511https://doaj.org/article/0e957108156f4ea585a2b4484c5cb0402013-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00437-13https://doaj.org/toc/2150-7511ABSTRACT 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.Vinai Chittezham ThomasLauren C. KinkeadAshley JanssenCarolyn R. SchaefferKeith M. WoodsJill K. LindgrenJonathan M. PeasterSujata S. ChaudhariMarat SadykovJoselyn JonesSameh M. Mohamadi AbdelGhaniMatthew C. ZimmermanKenneth W. BaylesGreg A. SomervillePaul D. FeyAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 4 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 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 A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness of <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> During β-Lactam Stress
description	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.
format	article
author	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
author_facet	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
author_sort	Vinai Chittezham Thomas
title	A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness of <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> During β-Lactam Stress
title_short	A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness of <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> During β-Lactam Stress
title_full	A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness of <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> During β-Lactam Stress
title_fullStr	A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness of <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> During β-Lactam Stress
title_full_unstemmed	A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness of <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> During β-Lactam Stress
title_sort	dysfunctional tricarboxylic acid cycle enhances fitness of <named-content content-type="genus-species">staphylococcus epidermidis</named-content> during β-lactam stress
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/0e957108156f4ea585a2b4484c5cb040
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A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness of <named-content content-type="genus-species">Staphylococcus epidermidis</named-content> During β-Lactam Stress

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