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

Authors

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

Document Type

Article

Journal Title

MBio

Publication Date

Summer 8-20-2013

Volume

4

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.

MeSH Headings

Anti-Bacterial Agents, Citric Acid Cycle, Humans, Microbial Sensitivity Tests, Microbial Viability, Oxacillin, Oxidative Stress, Reactive Oxygen Species, Staphylococcus epidermidis, beta-Lactams

DOI Link

10.1128/mBio.00437-13

ISSN

2150-7511

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.

Recommended Citation

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.; and Fey, Paul D., "A dysfunctional tricarboxylic acid cycle enhances fitness of Staphylococcus epidermidis during β-lactam stress." (2013). Journal Articles: Pathology and Microbiology. 15.
https://digitalcommons.unmc.edu/com_pathmicro_articles/15