Exposure to subinhibitory concentrations of penicillin increases optochin resistant phenotype in Streptococcus pneumoniae.

CORTES PR; PIÑAS GE; ALBARRACIN ORIO A; ECHENIQUE J

Pinamar

Congreso; XLI Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular,; 2005

SAIB

Optochin is an antibiotic utilized only for in vitro identification of pneumococcal isolates. Point mutations in atpC gene, which codify for a subunit of F0F1 ATPase, confer resistance to optochin (optR), and complicate the clinical diagnostic. Previously, we have characterized nine optR invasive strains, describing different atpC mutations. In this work, our aim was to analyse the putative causes of optochin resistance in S. pneumoniae. It's known that different stresses (hydrogen peroxide, antibiotics, etc) can increase the mutation rates in bacteria. In this sense, we exposed a wild-type strain to subinhibitory concentrations of different antibiotics, and we studied their impact on generation of optR strains. Remarkably, only penicillin was able to increase the optochin resistance rate. The penicillin-induced optR mutants were characterized and we found a wide range of atpC mutations that we could not find in clinical isolates. Probably, some atpC mutations alter the pneumococcal pathogenesis and they are lost during the infection process. To verify this hypothesis, we inoculated C57B mice with a pool of penicillin-induced optR mutants, and bacterial cells were recovered from liver. The atpC mutations were identified in 20 optR mutants selected at random, showing that most in vivo-selected mutants are identical to the optR mutants isolated from invasive diseases. We suggest that the mutation-rate increase due to penicillin exposition could be an adaptive strategy that we evidenced with the optochin resistance model in S. pneumoniae.