title: An examination of the inhibitory effects of three antibiotics in combination on ribosome biosynthesis in Staphylococcus aureus.
abstract: Although a number of different antibiotics are used to combat staphylococcal infections, resistance has continued to develop. The use of rifampicin and ciprofloxacin in combination with azithromycin, known for its inhibitory effects on the bacterial ribosome, can create potential synergistic effects on ribosomal subunit synthesis rates. In this work, combination antibiotic treatments gave a significant decrease in cell numbers following growth in the presence of ciprofloxacin or rifampicin with azithromycin compared to those grown with azithromycin or rifampicin alone. DNA, RNA and protein synthesis rates were reduced with single antibiotic treatments and showed further decreases when drug combinations were used. 70S ribosome levels were reduced with every antibiotic treatment. DNA gyrase subunits A and B showed significant decreases for double and triple antibiotic-treated samples. Ribosomal subunit synthesis rates were diminished for each different antibiotic combination. Turnover of 16S and 23S rRNA was also observed in each case and was stimulated by antibiotic combinations. The frequency of spontaneous resistance was reduced in all double selections, and no triply resistant mutants were found.
authors.affiliation: Department of Biomedical Sciences, J.H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Beach
authors.forename: W Scott
authors.initials: WS
authors.lastname: Champney
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D050296:Microbial Viability / Q000187:drug effects; D059645:Mutation Rate; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D012336:RNA, Ribosomal, 16S / Q000378:metabolism; D012338:RNA, Ribosomal, 23S / Q000378:metabolism; D054657:Ribosome Subunits / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S; D012338:RNA, Ribosomal, 23S