Subinhibitory concentrations of penicillin increase the mutation rate to optochin resistance in Streptococcus pneumoniae

• Published in: Journal of antimicrobial chemotherapy Vol. 62; no. 5; pp. 973 - 977
• Main Authors: Cortes, Paulo R., Piñas, Germán E., Albarracin Orio, Andrea G., Echenique, José R.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-11-2008; Oxford Publishing Limited (England)
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial diseases; Bacterial Proteins - genetics; Biological and medical sciences; DNA Mutational Analysis; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; DNA-Directed RNA Polymerases - genetics; Drug resistance; Drug Resistance, Bacterial; Human bacterial diseases; Humans; Infectious diseases; Medical sciences; mismatch repair system; Molecular Sequence Data; mutability; Mutagens - pharmacology; Mutation; Mutation, Missense; Penicillins - pharmacology; Pharmacology. Drug treatments; Proton-Translocating ATPases - genetics; Quinine - analogs & derivatives; Quinine - pharmacology; rifampicin; Sequence Analysis, DNA; Staphylococcal infections, streptococcal infections, pneumococcal infections; Streptococcus; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - drug effects; Streptococcus pneumoniae - genetics; rifampicin; mismatch repair system; mutability; β-Lactams; Mutability; Concentration; Streptococcus pneumoniae; Infection; Penicillin derivatives; Resistance; Streptococcaceae; Antibiotic; Base mismatching; Rifampicin; Streptococcal infection; Penicillin; Bacteriosis; Bacteria; Micrococcales; Genetics; Antituberculous agent; Protein synthesis inhibitor; Mutation; Antibacterial agent; Pneumococcal infection
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkn322

Objectives The aim of this work was to study the effect of subinhibitory concentrations of penicillin, chloramphenicol and erythromycin on the mutation rate of Streptococcus pneumoniae. Methods The mutation rate to rifampicin and optochin resistance was estimated using fluctuation analysis in three capsulated S. pneumoniae strains, cultured both with and without different subinhibitory antibiotic concentrations. The atpAC and rpoB mutations that conferred optochin and rifampicin resistance, respectively, were identified by DNA sequencing. Results The exposure to subinhibitory concentrations of penicillin increased the mutation rate (expressed as mutation per cell division) to optochin resistance between 2.1- and 3.1-fold for all three strains studied. In contrast, the rifampicin resistance assay showed no significant variations. To analyse the putative cause of the different responses between the optochin and rifampicin tests, mutations that conferred resistance in both cases were analysed. The difference may be explained by the genetic nature of the atpAC mutations, mostly transversions, which are not efficiently repaired by the HexAB mismatch repair system. Conclusions We demonstrated that subinhibitory concentrations of penicillin significantly increased the mutation rate of S. pneumoniae, suggesting that exposure to this antibiotic could help this pathogen to acquire mutations that confer resistance to other antibiotics. The optochin test was useful to detect this phenomenon and it should be considered for further mutability analysis in S. pneumoniae.