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.
  
  
  OBJECTIVE
  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.
authors: Department of Pathology and Microbiology, Center for Staphylococcal Research, Omaha, Nebraska, USA.
authors: Vinai C
authors: VC
authors: Thomas
authors: Department of Pathology and Microbiology, Center for Staphylococcal Research, Omaha, Nebraska, USA.
authors: Vinai
authors: V
authors: Chittezham Thomas
authors: Lauren C
authors: LC
authors: Kinkead
authors: Ashley
authors: A
authors: Janssen
authors: Carolyn R
authors: CR
authors: Schaeffer
authors: Keith M
authors: KM
authors: Woods
authors: Jill K
authors: JK
authors: Lindgren
authors: Jonathan M
authors: JM
authors: Peaster
authors: Sujata S
authors: SS
authors: Chaudhari
authors: Marat
authors: M
authors: Sadykov
authors: Joselyn
authors: J
authors: Jones
authors: Sameh M Mohamadi
authors: SM
authors: AbdelGhani
authors: Matthew C
authors: MC
authors: Zimmerman
authors: Kenneth W
authors: KW
authors: Bayles
authors: Greg A
authors: GA
authors: Somerville
authors: Paul D
authors: PD
authors: Fey
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002952:Citric Acid Cycle; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D010068:Oxacillin / Q000494:pharmacology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D017382:Reactive Oxygen Species; D047090:beta-Lactams; D010068:Oxacillin
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