Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains

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dc.contributor.authorTirado Vélez, Jose Manuel
dc.contributor.authorCarreño, David
dc.contributor.authorSevillano Fernández, David
dc.contributor.authorAlou Cervera, Luis
dc.contributor.authorYuste, José
dc.contributor.authorde la Campa, Adela G.
dc.date.accessioned2023-06-17T08:26:28Z
dc.date.available2023-06-17T08:26:28Z
dc.date.issued2021-05-13
dc.description.abstractAntibiotic resistance in Streptococcus pneumoniae 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; p < 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; p < 0.01) and higher values of area under the serum concentration-time curve (AUC0-12h of 17.3 vs. 5; p < 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.
dc.description.departmentDepto. de Medicina
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía, Industria y Competitividad
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/72086
dc.identifier.doi10.3390/antibiotics10050573
dc.identifier.issn2079-6382
dc.identifier.officialurlhttps://doi.org/10.3390/antibiotics10050573
dc.identifier.relatedurlhttps://www.mdpi.com/2079-6382/10/5/573
dc.identifier.urihttps://hdl.handle.net/20.500.14352/7123
dc.issue.number5
dc.journal.titleAntibiotics
dc.language.isoeng
dc.page.initial573
dc.publisherMPDI
dc.relation.projectID(grants BIO2017-82951-R and SAF2017-83388)
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.keywordStreptococcus pneumoniae
dc.subject.keywordDNA topoisomerase I inhibitor
dc.subject.keywordseconeolitsine
dc.subject.keywordresistance
dc.subject.keywordinvasive pneumococcal disease
dc.subject.ucmFarmacología (Medicina)
dc.subject.ucmInmunología
dc.subject.ucmOncología
dc.subject.unesco2412 Inmunología
dc.subject.unesco3201.01 Oncología
dc.titleSeconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains
dc.typejournal article
dc.volume.number10
dspace.entity.typePublication
relation.isAuthorOfPublication518c916a-df78-48cc-9bf7-6a2aaca7d6a2
relation.isAuthorOfPublication889e4dc3-c630-429e-be0f-7f0df2cff492
relation.isAuthorOfPublication.latestForDiscovery518c916a-df78-48cc-9bf7-6a2aaca7d6a2
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