title: Analysis of the tolerance of pathogenic enterococci and Staphylococcus aureus to cell wall active antibiotics.
abstract: OBJECTIVE
  Tolerance refers to the phenomenon that bacteria do not significantly die when exposed to bactericidal antibiotics. Enterococci are known for their high tolerance to these drugs, but the molecular reasons why they resist killing are not understood. In a previous study we showed that the superoxide dismutase (SOD) is implicated in this tolerance. This conclusion was based on the results obtained with one particular strain of Enterococcus faecalis and therefore the objective of the present communication was to analyse whether dependence of tolerance on active SOD is a general phenomenon for enterococci and another Gram-positive pathogen, Staphylococcus aureus.
  
  
  METHODS
  Mutants deficient in SOD activity were constructed in pathogenic enterococci. The wild-type sodA gene was cloned into an expression vector and transformed into SOD-deficient strains for complementation with varying levels of SOD activity. Previously constructed SOD-deficient strains of S. aureus were also included in this study. Tolerance to vancomycin and penicillin was then tested.
  
  
  RESULTS
  We demonstrated that the dependence on SOD of tolerance to vancomycin and penicillin is a common trait of antibiotic-susceptible pathogenic enterococci. By varying the levels of expression we could also show that tolerance to vancomycin is directly correlated to SOD activity. Interestingly, deletion of the sodA gene in a non-tolerant Enterococcus faecium strain did not further sensitize the mutant to bactericidal antibiotics. Finally, we showed that the SOD enzymes of S. aureus are also implicated in tolerance to vancomycin.
  
  
  CONCLUSIONS
  High tolerance of enterococci to cell wall active antibiotics can be reversed by SOD deficiency.
authors: Université de Caen Basse-Normandie, EA4655 U2RM-Stress and Virulence, F-14032 Caen, France. axel.hartke@unicaen.fr
authors: Rabia
authors: R
authors: Ladjouzi
authors: Alain
authors: A
authors: Bizzini
authors: François
authors: F
authors: Lebreton
authors: Nicolas
authors: N
authors: Sauvageot
authors: Alain
authors: A
authors: Rincé
authors: Abdellah
authors: A
authors: Benachour
authors: Axel
authors: A
authors: Hartke
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000187:drug effects*; D004361:Drug Tolerance; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000201:enzymology; D016984:Enterococcus faecium / Q000187:drug effects* / Q000201:enzymology; D017353:Gene Deletion; D005816:Genetic Complementation Test; D008826:Microbial Sensitivity Tests; D010406:Penicillins / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins; D014640:Vancomycin; D013482:Superoxide Dismutase
keywords: bactericidal antibiotics; oxidative stress; superoxide dismutases