A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness of Staphylococcus epidermidis During β-Lactam Stress

Authors

Vinai Chittenzham Thomas, Department of Pathology and Microbiology, Center for Staphylococcal Research
Lauren Kinkhead, Department of Pathology and Microbiology, Center for Staphylococcal Research
Ashley Janssen, Department of Pathology and Microbiology, Center for Staphylococcal Research
Carolyn Schaeffer, Department of Pathology and Microbiology, Center for Staphylococcal Research
Keith Woods, Department of Pathology and Microbiology, Center for Staphylococcal Research
Jill Lindgren, Department of Pathology and Microbiology, Center for Staphylococcal Research
Johnathan Peaster, Department of Pathology and Microbiology, Center for Staphylococcal Research
Sujata Chaudhari, Department of Pathology and Microbiology, Center for Staphylococcal Research
Marat Sadykov, Department of Pathology and Microbiology, Center for Staphylococcal Research
Joselyn Jones, Department of Cellular and Integrative Physiology
Sameh Mohamadi AbdelGhani, University of Nebraska Medical Center, Omaha, Nebraska, USA; Department of Microbiology and Immunology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
Matthew Zimmerman, Department of Cellular and Integrative Physiology
Kenneth W. Bayles, University of Nebraska Medical CenterFollow
Greg Somerville, University of Nebraska-LincolnFollow
Paul Fey, Department of Pathology and Microbiology, Center for Staphylococcal ResearchFollow

ORCID IDs

Kenneth W. Bayles

Date of this Version

2013

Citation

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 4(4):e00437-13. doi:10.1128/mBio.00437-13.

Comments

This article is a U.S. government work, and is not subject to copyright in the United States.

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.