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Original Paper

An examination of the inhibitory effects of three antibiotics in combination on ribosome biosynthesis in Staphylococcus aureus Justin M. Beach · W. Scott Champney 

Received: 10 January 2014 / Revised: 30 January 2014 / Accepted: 5 February 2014 © Springer-Verlag Berlin Heidelberg 2014

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.

Communicated by Erko Stackebrandt. Electronic supplementary material  The online version of this article (doi:10.1007/s00203-014-0963-5) contains supplementary material, which is available to authorized users. J. M. Beach · W. S. Champney (*)  Department of Biomedical Sciences, J.H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA e-mail: [email protected]

Keywords  Staphylococcus aureus · Azithromycin · Rifampicin · Ciprofloxacin · Ribosome synthesis

Introduction As a growing threat to public health, antibiotic resistance is a prevalent and increasing concern in the medical field (reviewed in (Davies and Davies 2010; Rosen 2011)). Excessive use of antibiotics for treating humans, animals or in agriculture is thought to be a major contributor to this problem (Mascaretti 2003; Walsh 2003). Bacteremia initiated by staphylococcal infections, particularly Staphylococcus aureus infections, can be a serious cause for alarm. Antibiotic resistance in species such as S. aureus was thought to be hospital acquired, but many studies have now shown that community-acquired infections are becoming more prevalent (Hawkey and Jones 2009). In order to fight this serious problem, novel antibiotics, new antibiotic targets and new methods to combat resistance are necessary. Antibiotic resistance can occur through several different mechanisms, including the modification of targets, the acquisition of genes conferring resistance, spontaneous mutations and the up-regulation of genes encoding c