Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains
Antibiotic resistance in <i>Streptococcus pneumoniae</i> has increased worldwide, making fluoroquinolones an alternative therapeutic option. Fluoroquinolones inhibit the type II DNA topoisomerases (topoisomerase IV and gyrase). In this study we have evaluated the in vivo activity of seco...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/5/573 |
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| author | Jose Manuel Tirado-Vélez David Carreño David Sevillano Luis Alou José Yuste Adela G. de la Campa |
| author_facet | Jose Manuel Tirado-Vélez David Carreño David Sevillano Luis Alou José Yuste Adela G. de la Campa |
| author_sort | Jose Manuel Tirado-Vélez |
| collection | DOAJ |
| description | Antibiotic resistance in <i>Streptococcus pneumoniae</i> has increased worldwide, making fluoroquinolones an alternative therapeutic option. Fluoroquinolones inhibit the type II DNA topoisomerases (topoisomerase IV and gyrase). In this study we have evaluated the in vivo activity of seconeolitsine, an inhibitor of topoisomerase I. Levofloxacin (12.5 to 50 mg/kg) or seconeolitsine (5 to 40 mg/kg) were administered every 12 h during two days in mice infected with a serotype 8-resistant strain. At 48 h, a 70% protection was obtained with seconeolitsine (40 mg/kg; <i>p</i> < 0.001). However, survival with levofloxacin was 20%, regardless of the dose. In addition, seconeolitsine decreased bacteremia efficiently. Levofloxacin had higher levels in serum than seconeolitsine (Cmax of 14.7 vs. 1.6; <i>p</i> < 0.01) and higher values of area under the serum concentration-time curve (AUC<sub>0-12h</sub> of 17.3 vs. 5; <i>p</i> < 0.01). However, seconeolitsine showed higher levels of time to peak concentration and elimination half-life. This is consistent with the higher binding of seconeolitsine to plasma proteins (40% and 80% when used at 1 µg/mL and 50 µg/mL, respectively) in comparison to levofloxacin (12% at 5 µg/mL and 33% at 50 µg/mL). Our results suggest that seconeolitsine would be a promising therapeutic alternative against pneumococcal isolates with high fluoroquinolone resistance levels. |
| first_indexed | 2024-03-10T11:27:43Z |
| format | Article |
| id | doaj.art-5b7a65b8d6b0468da794a1ec4d399a0f |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T11:27:43Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-5b7a65b8d6b0468da794a1ec4d399a0f2023-11-21T19:29:14ZengMDPI AGAntibiotics2079-63822021-05-0110557310.3390/antibiotics10050573Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant StrainsJose Manuel Tirado-Vélez0David Carreño1David Sevillano2Luis Alou3José Yuste4Adela G. de la Campa5Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, SpainCentro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, SpainMicrobiology Division-Department of Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainMicrobiology Division-Department of Medicine, Universidad Complutense de Madrid, 28040 Madrid, SpainCentro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, SpainCentro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, SpainAntibiotic resistance in <i>Streptococcus pneumoniae</i> has increased worldwide, making fluoroquinolones an alternative therapeutic option. Fluoroquinolones inhibit the type II DNA topoisomerases (topoisomerase IV and gyrase). In this study we have evaluated the in vivo activity of seconeolitsine, an inhibitor of topoisomerase I. Levofloxacin (12.5 to 50 mg/kg) or seconeolitsine (5 to 40 mg/kg) were administered every 12 h during two days in mice infected with a serotype 8-resistant strain. At 48 h, a 70% protection was obtained with seconeolitsine (40 mg/kg; <i>p</i> < 0.001). However, survival with levofloxacin was 20%, regardless of the dose. In addition, seconeolitsine decreased bacteremia efficiently. Levofloxacin had higher levels in serum than seconeolitsine (Cmax of 14.7 vs. 1.6; <i>p</i> < 0.01) and higher values of area under the serum concentration-time curve (AUC<sub>0-12h</sub> of 17.3 vs. 5; <i>p</i> < 0.01). However, seconeolitsine showed higher levels of time to peak concentration and elimination half-life. This is consistent with the higher binding of seconeolitsine to plasma proteins (40% and 80% when used at 1 µg/mL and 50 µg/mL, respectively) in comparison to levofloxacin (12% at 5 µg/mL and 33% at 50 µg/mL). Our results suggest that seconeolitsine would be a promising therapeutic alternative against pneumococcal isolates with high fluoroquinolone resistance levels.https://www.mdpi.com/2079-6382/10/5/573<i>Streptococcus pneumoniae</i>DNA topoisomerase I inhibitorseconeolitsineresistanceinvasive pneumococcal disease. |
| spellingShingle | Jose Manuel Tirado-Vélez David Carreño David Sevillano Luis Alou José Yuste Adela G. de la Campa Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains Antibiotics <i>Streptococcus pneumoniae</i> DNA topoisomerase I inhibitor seconeolitsine resistance invasive pneumococcal disease. |
| title | Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains |
| title_full | Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains |
| title_fullStr | Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains |
| title_full_unstemmed | Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains |
| title_short | Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains |
| title_sort | seconeolitsine the novel inhibitor of dna topoisomerase i protects against invasive pneumococcal disease caused by fluoroquinolone resistant strains |
| topic | <i>Streptococcus pneumoniae</i> DNA topoisomerase I inhibitor seconeolitsine resistance invasive pneumococcal disease. |
| url | https://www.mdpi.com/2079-6382/10/5/573 |
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