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

PAULO R. CORTES, GERMÁN E. PIÑAS, ANDREA G. ALBARRACÍN ORIO, AND JOSÉ ECHENIQUE

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY

Oxford University Press

Lugar: Oxford, Reino Unido; Año: 2008 p. 973 - 977

0305-7453

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 fluctuationanalysis in three capsulated S. pneumoniae strains, cultured both with and without different subinhibitoryantibiotic concentrations. The atpAC and rpoB mutations that conferred optochin and rifampicinresistance, 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 threestrains studied. In contrast, the rifampicin resistance assay showed no significant variations. Toanalyse 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 bythe genetic nature of the atpAC mutations, mostly transversions, which are not efficiently repaired bythe HexAB mismatch repair system.Conclusions: We demonstrated that subinhibitory concentrations of penicillin significantly increasedthe mutation rate of S. pneumoniae, suggesting that exposure to this antibiotic could help this pathogento acquire mutations that confer resistance to other antibiotics. The optochin test was useful todetect this phenomenon and it should be considered for further mutability analysis in S. pneumoniae.