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

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

来源：mBio, 2013, 4(4): e00437-13.

DOI：10.1128/mBio.00437-13

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 beta-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 beta-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. %26lt;br%26gt;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 beta-lactam antibiotics.

• 出版日期2013-8