Antibacterial activity of a DNA topoisomerase I inhibitor versus fluoroquinolones in Streptococcus pneumoniae
| Autor: | Patricia Mateos-Martínez, María Teresa Antonio García, Adela G. de la Campa, Mirian Domenech, Fernando González-Camacho, Myriam V. Valenzuela |
|---|---|
| Přispěvatelé: | Ministerio de Economía y Competitividad (España) |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Moxifloxacin Levofloxacin Pathology and Laboratory Medicine medicine.disease_cause Microbiología Biochemistry DNA gyrase Antibiotics Medicine and Health Sciences Enzyme Inhibitors Multidisciplinary biology Antimicrobials Pharmaceutics Chemistry Drugs Pneumococcus Antimicrobial Bacterial Pathogens Anti-Bacterial Agents Streptococcus pneumoniae Medical Microbiology DNA Gyrase Medicine Pathogens Research Article Fluoroquinolones medicine.drug DNA Topoisomerase IV Topoisomerase IV Science 030106 microbiology Topoisomerase-I Inhibitor Research and Analysis Methods Microbiology 03 medical and health sciences Drug Therapy Microbial Control medicine Benzodioxoles Molecular Biology Techniques Microbial Pathogens Molecular Biology Pharmacology Bacteria Topoisomerase Organisms Biology and Life Sciences Streptococcus Bacteriology Phenanthrenes biochemical phenomena metabolism and nutrition Genética 030104 developmental biology Biofilms Antibiotic Resistance Enzymology biology.protein Antimicrobial Resistance Topoisomerase I Inhibitors Bacterial Biofilms Cloning |
| Zdroj: | E-Prints Complutense: Archivo Institucional de la UCM Universidad Complutense de Madrid PLoS ONE Repisalud Instituto de Salud Carlos III (ISCIII) E-Prints Complutense. Archivo Institucional de la UCM instname PLoS ONE, Vol 15, Iss 11, p e0241780 (2020) |
| Popis: | The DNA topoisomerase complement of Streptococcus pneumoniae is constituted by two type II enzymes (topoisomerase IV and gyrase), and a single type I enzyme (topoisomerase I). These enzymes maintain the DNA topology, which is essential for replication and transcription. While fluoroquinolones target the type II enzymes, seconeolitsine, a new antimicrobial agent, targets topoisomerase I. We compared for the first time the in vitro effect of inhibition of topoisomerase I by seconeolitsine and of the type II topoisomerases by the fluoroquinolones levofloxacin and moxifloxacin. We used three isogenic non-encapsulated strains and five non-vaccine serotypes isolates belonging to two circulating pneumococcal clones, ST638 (2 strains) and ST1569V (3 strains). Each group contained strains with diverse susceptibility to fluoroquinolones. Minimal inhibitory concentrations, killing curves and postantibiotic effects were determined. Seconeolitsine demonstrated the fastest and highest bactericidal activity against planktonic bacteria and biofilms. When fluoroquinolone-susceptible planktonic bacteria were considered, seconeolitsine induced postantibiotic effects (1.00-1.87 h) similar than levofloxacin (1.00-2.22 h), but longer than moxifloxacin (0.39-1.71 h). The same effect was observed in sessile bacteria forming biofilms. Seconeolitsine induced postantibiotic effects (0.84-2.31 h) that were similar to those of levofloxacin (0.99-3.32 h) but longer than those of moxifloxacin (0.89-1.91 h). The greatest effect was observed in the viability and adherence of bacteria in the postantibiotic phase. Seconeolitsine greatly reduced the thickness of the biofilms formed in comparison with fluoroquinolones: 2.91 ± 0.43 μm (seconeolitsine), 7.18 ± 0.58 μm (levofloxacin), 17.08 ± 1.02 μm (moxifloxacin). When fluoroquinolone-resistant bacteria were considered, postantibiotic effects induced by levofloxacin and moxifloxacin, but not by seconeolitsine, were shorter, decreasing up to 5-fold (levofloxacin) or 2-fold (moxifloxacin) in planktonic cells, and up to 1.7 (levofloxacin) or 1.4-fold (moxifloxacin) during biofilm formation. Therefore, topoisomerase I inhibitors could be an alternative for the treatment of pneumococcal diseases, including those caused by fluoroquinolone-resistant isolates. This study was supported by grant BIO2017-82951-R from Plan Nacional de I+D+I of the Ministry of Economy and Competitiveness (to AGC). Sí |
| Databáze: | OpenAIRE |
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