Uptake of Ozenoxacin and Other Quinolones in Gram-Positive Bacteria
The big problem of antimicrobial resistance is that it requires great efforts in the design of improved drugs which can quickly reach their target of action. Studies of antibiotic uptake and interaction with their target it is a key factor in this important challenge. We investigated the accumulatio...
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| Veröffentlicht in: | International journal of molecular sciences 2021-12, Vol.22 (24), p.13363, Article 13363 |
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| creator | Lopez, Yuly Munoz, Laura Gargallo-Viola, Domingo Canton, Rafael Vila, Jordi Zsolt, Ilonka |
| description | The big problem of antimicrobial resistance is that it requires great efforts in the design of improved drugs which can quickly reach their target of action. Studies of antibiotic uptake and interaction with their target it is a key factor in this important challenge. We investigated the accumulation of ozenoxacin (OZN), moxifloxacin (MOX), levofloxacin (LVX), and ciprofloxacin (CIP) into the bacterial cells of 5 species, including Staphylococcus aureus (SA4-149), Staphylococcus epidermidis (SEP7602), Streptococcus pyogenes (SPY165), Streptococcus agalactiae (SAG146), and Enterococcus faecium (EF897) previously characterized.The concentration of quinolone uptake was estimated by agar disc-diffusion bioassay. Furthermore, we determined the inhibitory concentrations 50 (IC50) of OZN, MOX, LVX, and CIP against type II topoisomerases from S. aureus.The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The rapid penetration of OZN into the cell was reflected during the first minute of exposure with antibiotic values between 190 and 447 ng/mg (dry weight) of bacteria in all strains. Moreover, OZN showed the greatest inhibitory activity among the quinolones tested for both DNA gyrase and topoisomerase IV isolated from S. aureus with IC50 values of 10 and 0.5 mg/L, respectively. OZN intracellular concentration was significantly higher than that of MOX, LVX and CIP. All of these features may explain the higher in vitro activity of OZN compared to the other tested quinolones. |
| doi_str_mv | 10.3390/ijms222413363 |
| format | Article |
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Studies of antibiotic uptake and interaction with their target it is a key factor in this important challenge. We investigated the accumulation of ozenoxacin (OZN), moxifloxacin (MOX), levofloxacin (LVX), and ciprofloxacin (CIP) into the bacterial cells of 5 species, including Staphylococcus aureus (SA4-149), Staphylococcus epidermidis (SEP7602), Streptococcus pyogenes (SPY165), Streptococcus agalactiae (SAG146), and Enterococcus faecium (EF897) previously characterized.The concentration of quinolone uptake was estimated by agar disc-diffusion bioassay. Furthermore, we determined the inhibitory concentrations 50 (IC50) of OZN, MOX, LVX, and CIP against type II topoisomerases from S. aureus.The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The rapid penetration of OZN into the cell was reflected during the first minute of exposure with antibiotic values between 190 and 447 ng/mg (dry weight) of bacteria in all strains. Moreover, OZN showed the greatest inhibitory activity among the quinolones tested for both DNA gyrase and topoisomerase IV isolated from S. aureus with IC50 values of 10 and 0.5 mg/L, respectively. OZN intracellular concentration was significantly higher than that of MOX, LVX and CIP. All of these features may explain the higher in vitro activity of OZN compared to the other tested quinolones.</description><identifier>ISSN: 1661-6596</identifier><identifier>ISSN: 1422-0067</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms222413363</identifier><identifier>PMID: 34948159</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>Accumulation ; Aminopyridines - pharmacokinetics ; Aminopyridines - pharmacology ; Antibiotics ; Antimicrobial resistance ; Bacteria ; Bacterial Proteins - metabolism ; Bioassays ; Biochemistry & Molecular Biology ; Chemistry ; Chemistry, Multidisciplinary ; Ciprofloxacin ; DNA topoisomerase ; DNA topoisomerase IV ; Drug development ; Gram-positive bacteria ; Gram-Positive Bacteria - metabolism ; Levofloxacin ; Life Sciences & Biomedicine ; Molecular weight ; Moxifloxacin ; Mutation ; ozenoxacin ; Physical Sciences ; quinolone ; Quinolones ; Quinolones - pharmacokinetics ; Quinolones - pharmacology ; Science & Technology ; Staphylococcus aureus ; Staphylococcus infections ; Topoisomerase I Inhibitors - pharmacokinetics ; Topoisomerase I Inhibitors - pharmacology ; uptake</subject><ispartof>International journal of molecular sciences, 2021-12, Vol.22 (24), p.13363, Article 13363</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>3</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000738544800001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c481t-760e2885d38c1521ff85861b8479cfb20613357fdde33dbdd5e286c24245c40e3</citedby><cites>FETCH-LOGICAL-c481t-760e2885d38c1521ff85861b8479cfb20613357fdde33dbdd5e286c24245c40e3</cites><orcidid>0000-0003-1675-3173 ; 0000-0002-8900-722X ; 0000-0002-8025-3926</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708121/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708121/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34948159$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lopez, Yuly</creatorcontrib><creatorcontrib>Munoz, Laura</creatorcontrib><creatorcontrib>Gargallo-Viola, Domingo</creatorcontrib><creatorcontrib>Canton, Rafael</creatorcontrib><creatorcontrib>Vila, Jordi</creatorcontrib><creatorcontrib>Zsolt, Ilonka</creatorcontrib><title>Uptake of Ozenoxacin and Other Quinolones in Gram-Positive Bacteria</title><title>International journal of molecular sciences</title><addtitle>INT J MOL SCI</addtitle><addtitle>Int J Mol Sci</addtitle><description>The big problem of antimicrobial resistance is that it requires great efforts in the design of improved drugs which can quickly reach their target of action. Studies of antibiotic uptake and interaction with their target it is a key factor in this important challenge. We investigated the accumulation of ozenoxacin (OZN), moxifloxacin (MOX), levofloxacin (LVX), and ciprofloxacin (CIP) into the bacterial cells of 5 species, including Staphylococcus aureus (SA4-149), Staphylococcus epidermidis (SEP7602), Streptococcus pyogenes (SPY165), Streptococcus agalactiae (SAG146), and Enterococcus faecium (EF897) previously characterized.The concentration of quinolone uptake was estimated by agar disc-diffusion bioassay. Furthermore, we determined the inhibitory concentrations 50 (IC50) of OZN, MOX, LVX, and CIP against type II topoisomerases from S. aureus.The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The rapid penetration of OZN into the cell was reflected during the first minute of exposure with antibiotic values between 190 and 447 ng/mg (dry weight) of bacteria in all strains. Moreover, OZN showed the greatest inhibitory activity among the quinolones tested for both DNA gyrase and topoisomerase IV isolated from S. aureus with IC50 values of 10 and 0.5 mg/L, respectively. OZN intracellular concentration was significantly higher than that of MOX, LVX and CIP. All of these features may explain the higher in vitro activity of OZN compared to the other tested quinolones.</description><subject>Accumulation</subject><subject>Aminopyridines - pharmacokinetics</subject><subject>Aminopyridines - pharmacology</subject><subject>Antibiotics</subject><subject>Antimicrobial resistance</subject><subject>Bacteria</subject><subject>Bacterial Proteins - metabolism</subject><subject>Bioassays</subject><subject>Biochemistry & Molecular Biology</subject><subject>Chemistry</subject><subject>Chemistry, Multidisciplinary</subject><subject>Ciprofloxacin</subject><subject>DNA topoisomerase</subject><subject>DNA topoisomerase IV</subject><subject>Drug development</subject><subject>Gram-positive bacteria</subject><subject>Gram-Positive Bacteria - metabolism</subject><subject>Levofloxacin</subject><subject>Life Sciences & Biomedicine</subject><subject>Molecular weight</subject><subject>Moxifloxacin</subject><subject>Mutation</subject><subject>ozenoxacin</subject><subject>Physical Sciences</subject><subject>quinolone</subject><subject>Quinolones</subject><subject>Quinolones - pharmacokinetics</subject><subject>Quinolones - pharmacology</subject><subject>Science & Technology</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus infections</subject><subject>Topoisomerase I Inhibitors - pharmacokinetics</subject><subject>Topoisomerase I Inhibitors - pharmacology</subject><subject>uptake</subject><issn>1661-6596</issn><issn>1422-0067</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>DOA</sourceid><recordid>eNqNkU1rVDEUhoMoto4u3coFl3Jtvm-yEfRSa6EwCnYdcvPRZpxJxiS3Wn-9qdMOzq6rHJLnPCeHF4DXCL4nRMKTsNoUjDFFhHDyBBwjinEPIR-etppz1HMm-RF4UcoKQkwwk8_BEaGSCsTkMRgvt1X_cF3y3fKPi-m3NiF2OtpuWa9d7r7NIaZ1iq507f4s603_NZVQw43rPmlTXQ76JXjm9bq4V_fnAlx-Pv0-fukvlmfn48eL3rRhtR84dFgIZokwiGHkvWCCo0nQQRo_YcjbDmzw1jpC7GQtazg3mGLKDIWOLMD5zmuTXqltDhudb1XSQf27SPlK6VyDWTslkDBy4EwQKCjxQkNrPNPESM2kn0hzfdi5tvO0cda4WLNeH0gPX2K4VlfpRokBCoRRE7y9F-T0c3alqlWac2z7K8wRFpDKFsgC9DvK5FRKdn4_AUF1l586yK_xb_7_1p5-CKwBYgf8clPyxQQXjdtjEMKBCEapaBVEY6i6hhTHNMfaWt89vpX8BaZptjE</recordid><startdate>20211212</startdate><enddate>20211212</enddate><creator>Lopez, Yuly</creator><creator>Munoz, Laura</creator><creator>Gargallo-Viola, Domingo</creator><creator>Canton, Rafael</creator><creator>Vila, Jordi</creator><creator>Zsolt, Ilonka</creator><general>Mdpi</general><general>MDPI AG</general><general>MDPI</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-1675-3173</orcidid><orcidid>https://orcid.org/0000-0002-8900-722X</orcidid><orcidid>https://orcid.org/0000-0002-8025-3926</orcidid></search><sort><creationdate>20211212</creationdate><title>Uptake of Ozenoxacin and Other Quinolones in Gram-Positive Bacteria</title><author>Lopez, Yuly ; 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Studies of antibiotic uptake and interaction with their target it is a key factor in this important challenge. We investigated the accumulation of ozenoxacin (OZN), moxifloxacin (MOX), levofloxacin (LVX), and ciprofloxacin (CIP) into the bacterial cells of 5 species, including Staphylococcus aureus (SA4-149), Staphylococcus epidermidis (SEP7602), Streptococcus pyogenes (SPY165), Streptococcus agalactiae (SAG146), and Enterococcus faecium (EF897) previously characterized.The concentration of quinolone uptake was estimated by agar disc-diffusion bioassay. Furthermore, we determined the inhibitory concentrations 50 (IC50) of OZN, MOX, LVX, and CIP against type II topoisomerases from S. aureus.The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The accumulation of OZN inside the bacterial cell was superior in comparison to MOX, LVX, and CIP in all tested species. The rapid penetration of OZN into the cell was reflected during the first minute of exposure with antibiotic values between 190 and 447 ng/mg (dry weight) of bacteria in all strains. Moreover, OZN showed the greatest inhibitory activity among the quinolones tested for both DNA gyrase and topoisomerase IV isolated from S. aureus with IC50 values of 10 and 0.5 mg/L, respectively. OZN intracellular concentration was significantly higher than that of MOX, LVX and CIP. All of these features may explain the higher in vitro activity of OZN compared to the other tested quinolones.</abstract><cop>BASEL</cop><pub>Mdpi</pub><pmid>34948159</pmid><doi>10.3390/ijms222413363</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-1675-3173</orcidid><orcidid>https://orcid.org/0000-0002-8900-722X</orcidid><orcidid>https://orcid.org/0000-0002-8025-3926</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Accumulation Aminopyridines - pharmacokinetics Aminopyridines - pharmacology Antibiotics Antimicrobial resistance Bacteria Bacterial Proteins - metabolism Bioassays Biochemistry & Molecular Biology Chemistry Chemistry, Multidisciplinary Ciprofloxacin DNA topoisomerase DNA topoisomerase IV Drug development Gram-positive bacteria Gram-Positive Bacteria - metabolism Levofloxacin Life Sciences & Biomedicine Molecular weight Moxifloxacin Mutation ozenoxacin Physical Sciences quinolone Quinolones Quinolones - pharmacokinetics Quinolones - pharmacology Science & Technology Staphylococcus aureus Staphylococcus infections Topoisomerase I Inhibitors - pharmacokinetics Topoisomerase I Inhibitors - pharmacology uptake |
| title | Uptake of Ozenoxacin and Other Quinolones in Gram-Positive Bacteria |
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