Inhibition of <i>Staphylococcus pseudintermedius</i> Efflux Pumps by Using <i>Staphylococcus aureus</i> NorA Efflux Pump Inhibitors
One promising approach in treating antibiotic-resistant bacteria is to “break” resistances connected with antibacterial efflux by co-administering efflux pump inhibitors (EPIs) with antibiotics. Here, ten compounds, previously optimized to restore the susceptibility to ciprofloxacin (CIP) of <i&g...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/12/5/806 |
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| author | Elisa Rampacci Tommaso Felicetti Giada Cernicchi Valentina Stefanetti Stefano Sabatini Fabrizio Passamonti |
| author_facet | Elisa Rampacci Tommaso Felicetti Giada Cernicchi Valentina Stefanetti Stefano Sabatini Fabrizio Passamonti |
| author_sort | Elisa Rampacci |
| collection | DOAJ |
| description | One promising approach in treating antibiotic-resistant bacteria is to “break” resistances connected with antibacterial efflux by co-administering efflux pump inhibitors (EPIs) with antibiotics. Here, ten compounds, previously optimized to restore the susceptibility to ciprofloxacin (CIP) of <i>norA</i>-overexpressing <i>Staphylococcus aureus</i>, were evaluated for their ability to inhibit <i>norA</i>-mediated efflux in <i>Staphylococcus pseudintermedius</i> and synergize with CIP, ethidium bromide (EtBr), gentamycin (GEN), and chlorhexidine digluconate (CHX). We focused efforts on <i>S. pseudintermedius</i> as a pathogenic bacterium of concern within veterinary and human medicine. By combining data from checkerboard assays and EtBr efflux inhibition experiments, the hits 2-arylquinoline <b>1</b>, dihydropyridine <b>6,</b> and 2-phenyl-4-carboxy-quinoline <b>8</b> were considered the best EPIs for <i>S. pseudintermedius</i>. Overall, most of the compounds, except for 2-arylquinoline compound <b>2</b>, were able to fully restore the susceptibility of <i>S. pseudintermedius</i> to CIP and synergize with GEN as well, while the synergistic effect with CHX was less significant and often did not show a dose-dependent effect. These are valuable data for medicinal chemistry optimization of EPIs for <i>S. pseudintermedius</i> and lay the foundation for further studies on successful EPIs to treat staphylococcal infections. |
| first_indexed | 2024-03-11T04:00:14Z |
| format | Article |
| id | doaj.art-07aa8ef289f24530ab0c6a1e8f0c700a |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-11T04:00:14Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-07aa8ef289f24530ab0c6a1e8f0c700a2023-11-18T00:11:30ZengMDPI AGAntibiotics2079-63822023-04-0112580610.3390/antibiotics12050806Inhibition of <i>Staphylococcus pseudintermedius</i> Efflux Pumps by Using <i>Staphylococcus aureus</i> NorA Efflux Pump InhibitorsElisa Rampacci0Tommaso Felicetti1Giada Cernicchi2Valentina Stefanetti3Stefano Sabatini4Fabrizio Passamonti5Department of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, ItalyDepartment of Pharmaceutical Sciences, Via Del Liceo 1, 06123 Perugia, ItalyDepartment of Pharmaceutical Sciences, Via Del Liceo 1, 06123 Perugia, ItalyDepartment of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, ItalyDepartment of Pharmaceutical Sciences, Via Del Liceo 1, 06123 Perugia, ItalyDepartment of Veterinary Medicine, University of Perugia, Via San Costanzo 4, 06126 Perugia, ItalyOne promising approach in treating antibiotic-resistant bacteria is to “break” resistances connected with antibacterial efflux by co-administering efflux pump inhibitors (EPIs) with antibiotics. Here, ten compounds, previously optimized to restore the susceptibility to ciprofloxacin (CIP) of <i>norA</i>-overexpressing <i>Staphylococcus aureus</i>, were evaluated for their ability to inhibit <i>norA</i>-mediated efflux in <i>Staphylococcus pseudintermedius</i> and synergize with CIP, ethidium bromide (EtBr), gentamycin (GEN), and chlorhexidine digluconate (CHX). We focused efforts on <i>S. pseudintermedius</i> as a pathogenic bacterium of concern within veterinary and human medicine. By combining data from checkerboard assays and EtBr efflux inhibition experiments, the hits 2-arylquinoline <b>1</b>, dihydropyridine <b>6,</b> and 2-phenyl-4-carboxy-quinoline <b>8</b> were considered the best EPIs for <i>S. pseudintermedius</i>. Overall, most of the compounds, except for 2-arylquinoline compound <b>2</b>, were able to fully restore the susceptibility of <i>S. pseudintermedius</i> to CIP and synergize with GEN as well, while the synergistic effect with CHX was less significant and often did not show a dose-dependent effect. These are valuable data for medicinal chemistry optimization of EPIs for <i>S. pseudintermedius</i> and lay the foundation for further studies on successful EPIs to treat staphylococcal infections.https://www.mdpi.com/2079-6382/12/5/806antibiotic resistance breakersantimicrobial resistanceefflux pump inhibitorsNorA<i>Staphylococcus pseudintermedius</i><i>Staphylococcus aureus</i> |
| spellingShingle | Elisa Rampacci Tommaso Felicetti Giada Cernicchi Valentina Stefanetti Stefano Sabatini Fabrizio Passamonti Inhibition of <i>Staphylococcus pseudintermedius</i> Efflux Pumps by Using <i>Staphylococcus aureus</i> NorA Efflux Pump Inhibitors Antibiotics antibiotic resistance breakers antimicrobial resistance efflux pump inhibitors NorA <i>Staphylococcus pseudintermedius</i> <i>Staphylococcus aureus</i> |
| title | Inhibition of <i>Staphylococcus pseudintermedius</i> Efflux Pumps by Using <i>Staphylococcus aureus</i> NorA Efflux Pump Inhibitors |
| title_full | Inhibition of <i>Staphylococcus pseudintermedius</i> Efflux Pumps by Using <i>Staphylococcus aureus</i> NorA Efflux Pump Inhibitors |
| title_fullStr | Inhibition of <i>Staphylococcus pseudintermedius</i> Efflux Pumps by Using <i>Staphylococcus aureus</i> NorA Efflux Pump Inhibitors |
| title_full_unstemmed | Inhibition of <i>Staphylococcus pseudintermedius</i> Efflux Pumps by Using <i>Staphylococcus aureus</i> NorA Efflux Pump Inhibitors |
| title_short | Inhibition of <i>Staphylococcus pseudintermedius</i> Efflux Pumps by Using <i>Staphylococcus aureus</i> NorA Efflux Pump Inhibitors |
| title_sort | inhibition of i staphylococcus pseudintermedius i efflux pumps by using i staphylococcus aureus i nora efflux pump inhibitors |
| topic | antibiotic resistance breakers antimicrobial resistance efflux pump inhibitors NorA <i>Staphylococcus pseudintermedius</i> <i>Staphylococcus aureus</i> |
| url | https://www.mdpi.com/2079-6382/12/5/806 |
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