Respiratory burst induces tolerance to fluoroquinolones in Streptococcus pneumoniae.

HERNANDEZ MORFA, MIRELYS; VICTORIA ZAPPIA; CORTES PR; NICOLAS REINOSO; ECHENIQUE, J

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Congreso; Reunión Anual de la Sociedad Argentina de Microbiologia General; 2021

Sociedad Argentina de Microbiologia General

Streptococcus pneumoniae (Spn) is a major bacterial pathogen that usually colonizes the upper respiratory tract and causes pneumonia, bacteremia, and meningitis in humans. When a bacterial population is exposed to environmental stresses, such as oxidative stress, different subpopulations of cells with atypical phenotypes can usually be observed. Tolerant bacteria are a clonal subpopulation of cells that show an unusual ability to tolerate antibiotics, and it plays an important role in antibacterial therapies. However, antibiotic tolerance had not yet been described in S. pneumoniae. The main purpose of our work was to determine the induction of tolerance to fluoroquinolones (FQ) in cultures of Spn, as well as the impact of intracellular oxidative stress induced by lung epithelial cells and macrophages infected by Spn. When these eukaryotic cells were infected with the wild-type Spn strain, we found induction of FQ-tolerance, suggesting that the respiratory burst of macrophages and pneumocytes could be involved in this mechanism. To determine the contribution of oxidative stress genes in the formation of FQ-tolerant pneumococci, we mutated genes encoding for enzymes involved in the mechanism of oxidative stress resistance, such as sodA (encodes for a superoxide dismutase that degrades superoxides), tpxD (encodes for a peroxiredoxin that degrades H2O2) and spxB (encodes for pyruvate oxidase and is a major contributor of H2O2 production in Spn). The three mutants showed a decreased FQ tolerance in bacterial cultures, as well as in macrophages and pneumocytes, demonstrating that sodA, tpxD, and spxB play an important role in the mechanism of FQ tolerance in Spn. Here, we describe for the first time the formation of FQ tolerance in Spn, and we demonstrate that the mechanism of oxidative stress resistance is involved in the induction of FQ tolerance in Spn.