CONICET | Buscador de Institutos y Recursos Humanos

Bacterial persisters are a clonal subpopulation of bacterial cells that shows arrested or slow growth, and a decreased susceptibility to bactericidalantibiotics. Streptococcus pneumoniae is a main bacterial pathogen that usually colonizes the upper respiratory tract and causes pneumonia,bacteremia, and meningitis. The persistence phenomenon had not been described in S. pneumoniae. The main aim of our work was to determinethe formation of persisters in a population of S. pneumoniae in the presence of fluoroquinolones, as well as the impact of acidic and oxidativestress conditions. In this work, we found that the wild-type strain formed persisters to fluoroquinolones when cells were preincubated with H2O2,however this phenomenon was not detected under acidic conditions, suggesting that oxidative stress is involved in this mechanism. With thepurpose to determine the contribution of oxidative stress genes in the formation of persisters to fluoroquinolones, we mutated genes coding forenzymes involved in the mechanism of oxidative stress resistance, such as such as sodA (codes for a superoxide dismutase that degradessuperoxides), tpxD (codes for peroxiredoxine that degrades H2O2) y nrdH (codes for a peroxiredoxine that degrades H2O2). The three mutantswere incubated with H2O2 and then with fluoroquinolones, and the sodA and nrdH mutants showed no formation of persisters, while the tpxDmutant showed a similar phenotype to the wild-type strain.Here, we described for the first time the formation of persisters to antibiotics in S. pneumoniae, particularly persisters to fluoroquinolones. Inaddition, we demonstrated that the formation of persisters is associated with the mechanism of oxidative stress resistance.