OXIDATIVE STRESS CONDITIONS INDUCE PERSISTENCE TO FLUOROQUINOLONES IN Streptococcus pneumoniae

Salta

Encuentro; LV Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2019

SAIB

Bacterial persisters are a clonal subpopulation of bacterial cells that shows arrested or slow growth, and a decreased susceptibility to bactericidal antibiotics. 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 determine the formation of persisters in a population of S. pneumoniae in the presence of fluoroquinolones, as well as the impact of acidic and oxidative stress 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 the purpose to determine the contribution of oxidative stress genes in the formation of persisters to fluoroquinolones, we mutated genes coding for enzymes involved in the mechanism of oxidative stress resistance, such as such as sodA (codes for a superoxide dismutase that degrades superoxides), tpxD (codes for peroxiredoxine that degrades H2O2) y nrdH (codes for a peroxiredoxine that degrades H2O2). The three mutants were incubated with H2O2 and then with fluoroquinolones, and the sodA and nrdH mutants showed no formation of persisters, while the tpxD mutant 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. In addition, we demonstrated that the formation of persisters is associated with the mechanism of oxidative stress resistance.