title: Effect of clpP and clpC deletion on persister cell number in Staphylococcus aureus.
abstract: Staphylococcus aureus is responsible for a wide variety of infections that include superficial skin and soft tissue infections, septicaemia, central nervous system infections, endocarditis, osteomyelitis and pneumonia. Others have demonstrated the importance of toxin-antitoxin (TA) modules in the formation of persisters and the role of the Clp proteolytic system in the regulation of these TA modules. This study was conducted to determine the effect of clpP and clpC deletion on S. aureus persister cell numbers following antibiotic treatment. Deletion of clpP resulted in a significant decrease in persister cells following treatment with oxacillin and erythromycin but not with levofloxacin and daptomycin. Deletion of clpC resulted in a decrease in persister cells following treatment with oxacillin. These differences were dependent on the antibiotic class and the CFU ml-1 in which the cells were treated. Persister revival assays for all the bacterial strains in these studies demonstrated a significant delay in resumption of growth characteristic of persister cells, indicating that the surviving organisms in this study were not likely due to spontaneous antibiotic resistance. Based on our results, ClpP and possibly ClpC play a role in persister cell formation or maintenance, and this effect is dependent on antibiotic class and the CFU ml-1 or the growth phase of the cells.
authors.affiliation: Department of Microbiology/Immunology, A.T. Still University of Health Sciences, Kirksville College of Osteopathic Medicine, Kirksville, MO, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Springer
authors.affiliation: Department of Microbiology/Immunology, A.T. Still University of Health Sciences, Kirksville College of Osteopathic Medicine, Kirksville, MO, USA.
authors.forename: Vineet K
authors.initials: VK
authors.lastname: Singh
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Ambrose L
authors.initials: AL
authors.lastname: Cheung
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Niles P
authors.initials: NP
authors.lastname: Donegan
authors.affiliation: Department of Microbiology/Immunology, A.T. Still University of Health Sciences, Kirksville College of Osteopathic Medicine, Kirksville, MO, USA.
authors.forename: Neal R
authors.initials: NR
authors.lastname: Chamberlain
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D050296:Microbial Viability / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C087481:ClpC protein, Bacteria; D006360:Heat-Shock Proteins