Reactive Oxygen Species Production Is a Major Factor Directing the Postantibiotic Effect of Fluoroquinolones in Streptococcus pneumoniae
| Autor: | María-José Ferrándiz, M. V. Valenzuela, María Teresa Antonio García, A. G. de la Campa |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Moxifloxacin
chemistry.chemical_element Levofloxacin Microbial Sensitivity Tests medicine.disease_cause Oxygen Microbiology 03 medical and health sciences Mechanisms of Resistance Streptococcus pneumoniae medicine Pharmacology (medical) heterocyclic compounds Fragmentation (cell biology) DNA Cleavage 030304 developmental biology Pharmacology chemistry.chemical_classification 0303 health sciences Reactive oxygen species Strain (chemistry) biology 030306 microbiology biochemical phenomena metabolism and nutrition biology.organism_classification bacterial infections and mycoses Infectious Diseases chemistry Reactive Oxygen Species Bacteria medicine.drug Fluoroquinolones |
| Zdroj: | Repisalud Instituto de Salud Carlos III (ISCIII) |
| Popis: | We studied the molecular mechanisms involved in the postantibiotic effect of the fluoroquinolones levofloxacin and moxifloxacin in Streptococcus pneumoniae Wild-type strain R6 had postantibiotic effects of 2.05 ± 0.10 h (mean ± standard deviation [SD]) and 3.23 ± 0.45 h at 2.5× and 10× MIC of levofloxacin, respectively. Moxifloxacin exhibited lower effects of 0.87 ± 0.1 and 2.41 ± 0.29 h at 2.5× and 10× MIC, respectively. Fluoroquinolone-induced chromosome fragmentation was measured at equivalent postantibiotic effects for levofloxacin (2.5× MIC) and moxifloxacin (10× MIC). After 2 h of drug removal, reductions were approximately 7-fold for levofloxacin and 3-fold for moxifloxacin, without further decreases at later times. Variations in reactive oxygen species production were detected after 4 to 6 h of drug withdrawals, with decreases ≥400-fold for levofloxacin and ≥800-fold for moxifloxacin at 6 h. In accordance, after 4 to 6 h of drug withdrawal, the levofloxacin-induced upregulation of the fatCDEB operon, introducing iron in the bacteria, decreased up to 2- to 3-fold, and the moxifloxacin-induced upregulation of several genes involved in the production of pyruvate was reduced 3- to 7-fold. In accordance, lower postantibiotic effects (up to 1 h) were observed in strain R6 ΔspxB, lacking the main enzyme involved in oxygen peroxide production, than in R6. Although no change in the recovery of chromosome fragmentation was observed between R6 and R6 ΔspxB, 3.5 × 103-fold lower reactive oxygen species production was observed in R6 ΔspxB, without changes after drug removal. These results show that reactive oxygen species are the main factors directing the postantibiotic effect of levofloxacin and moxifloxacin in S. pneumoniae. This study was supported by grant BIO2017-82951-R from Plan Nacional de I+D+I of the Ministry of Economy and Competitiveness. Sí |
| Databáze: | OpenAIRE |
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