Inhibition of Ribosomal Subunit Synthesis in Escherichia coli by the Vanadyl Ribonucleoside Complex

The increase in antibiotic resistant microorganisms has driven a search for new antibiotic targets and novel antimicrobial agents. A large number of different antibiotics target bacterial ribosomal subunit formation. Several specific ribonucleases are important in the processing of rRNA during subunit biogenesis. This work demonstrates that the ribonuclease inhibitor, vanadyl ribonucleoside complex (VRC), can inhibit RNases involved in ribosomal subunit formation. The ribosomal subunit synthesis rate was significantly decreased and ribosomal RNA from the subunit precursors was degraded. VRC had no inhibitory effect on translation. VRC also potentiated the inhibitory effects of an aminoglycoside and a macrolide antibiotic

An examination of the inhibitory effects of three antibiotics in combination on ribosome biosynthesis in Staphylococcus aureus

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