Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against <i>Staphylococcus aureus</i> Strains
The bacterial species <i>Staphylococcus aureus</i> presents a variety of resistance mechanisms, among which the expression of β-lactamases and efflux pumps stand out for providing a significant degree of resistance to clinically relevant antibiotics. The 1,8-naphthyridines are nitrogen h...
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MDPI AG
2023-02-01
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| Online Access: | https://www.mdpi.com/1420-3049/28/4/1819 |
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| author | Cícera Datiane de Morais Oliveira-Tintino Saulo Relison Tintino Ana Carolina Justino de Araújo Cristina Rodrigues dos Santos Barbosa Priscilla Ramos Freitas José Bezerra de Araújo Neto Iêda Maria Begnini Ricardo Andrade Rebelo Luiz Everson da Silva Sandro Lucio Mireski Michele Caroline Nasato Maria Isabel Lacowicz Krautler Humberto Medeiros Barreto Jaime Ribeiro-Filho Irwin Rose Alencar de Menezes Henrique Douglas Melo Coutinho |
| author_facet | Cícera Datiane de Morais Oliveira-Tintino Saulo Relison Tintino Ana Carolina Justino de Araújo Cristina Rodrigues dos Santos Barbosa Priscilla Ramos Freitas José Bezerra de Araújo Neto Iêda Maria Begnini Ricardo Andrade Rebelo Luiz Everson da Silva Sandro Lucio Mireski Michele Caroline Nasato Maria Isabel Lacowicz Krautler Humberto Medeiros Barreto Jaime Ribeiro-Filho Irwin Rose Alencar de Menezes Henrique Douglas Melo Coutinho |
| author_sort | Cícera Datiane de Morais Oliveira-Tintino |
| collection | DOAJ |
| description | The bacterial species <i>Staphylococcus aureus</i> presents a variety of resistance mechanisms, among which the expression of β-lactamases and efflux pumps stand out for providing a significant degree of resistance to clinically relevant antibiotics. The 1,8-naphthyridines are nitrogen heterocycles with a broad spectrum of biological activities and, as such, are promising research targets. However, the potential roles of these compounds on bacterial resistance management remain to be better investigated. Therefore, the present study evaluated the antibacterial activity of 1,8-naphthyridine sulfonamides, addressing their ability to act as inhibitors of β-lactamases and efflux pump (QacA/B and QacC) against the strains SA-K4414 and SA-K4100 of <i>S. aureus</i>. All substances were prepared at an initial concentration of 1024 μg/mL, and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. Subsequently, their effects on β-lactamase- and efflux pump-mediated antibiotic resistance was evaluated from the reduction of the MIC of ethidium bromide (EtBr) and β-lactam antibiotics, respectively. The 1,8-naphthyridines did not present direct antibacterial activity against the strains SA-K4414 and SA-K4100 of <i>S. aureus</i>. On the other hand, when associated with antibiotics against both strains, the compounds reduced the MIC of EtBr and β-lactam antibiotics, suggesting that they may act by inhibiting β-lactamases and efflux pumps such as QacC and QacA/B. However, further research is required to elucidate the molecular mechanisms underlying these observed effects. |
| first_indexed | 2024-03-11T08:21:10Z |
| format | Article |
| id | doaj.art-97f794b19ec74d53a8e1ba7a399da1d8 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T08:21:10Z |
| publishDate | 2023-02-01 |
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| spelling | doaj.art-97f794b19ec74d53a8e1ba7a399da1d82023-11-16T22:23:39ZengMDPI AGMolecules1420-30492023-02-01284181910.3390/molecules28041819Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against <i>Staphylococcus aureus</i> StrainsCícera Datiane de Morais Oliveira-Tintino0Saulo Relison Tintino1Ana Carolina Justino de Araújo2Cristina Rodrigues dos Santos Barbosa3Priscilla Ramos Freitas4José Bezerra de Araújo Neto5Iêda Maria Begnini6Ricardo Andrade Rebelo7Luiz Everson da Silva8Sandro Lucio Mireski9Michele Caroline Nasato10Maria Isabel Lacowicz Krautler11Humberto Medeiros Barreto12Jaime Ribeiro-Filho13Irwin Rose Alencar de Menezes14Henrique Douglas Melo Coutinho15Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, CE, BrazilLaboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, CE, BrazilLaboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, CE, BrazilLaboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, CE, BrazilLaboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, CE, BrazilLaboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, CE, BrazilDepartment of Chemistry, Regional University of Blumenau (FURB), Itoupava Seca, Blumenau 89030-903, SC, BrazilDepartment of Chemistry, Regional University of Blumenau (FURB), Itoupava Seca, Blumenau 89030-903, SC, BrazilPostgraduate Program in Sustainable Territorial Development, Coastal Sector, Federal University of Paraná (UFPR), Curitiba 81531-990, PR, BrazilDepartment of Chemistry, Regional University of Blumenau (FURB), Itoupava Seca, Blumenau 89030-903, SC, BrazilDepartment of Chemistry, Regional University of Blumenau (FURB), Itoupava Seca, Blumenau 89030-903, SC, BrazilDepartment of Chemistry, Regional University of Blumenau (FURB), Itoupava Seca, Blumenau 89030-903, SC, BrazilLaboratory of Microbiology, Federal University of Piaui (UFPI), Teresina 64049-550, PI, BrazilOswaldo Cruz Foundation (Fiocruz), Fiocruz Ceará, Eusébio 60180-900, CE, BrazilLaboratory of Pharmacology and Molecular Chemistry (LFQM), Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, CE, BrazilLaboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, CE, BrazilThe bacterial species <i>Staphylococcus aureus</i> presents a variety of resistance mechanisms, among which the expression of β-lactamases and efflux pumps stand out for providing a significant degree of resistance to clinically relevant antibiotics. The 1,8-naphthyridines are nitrogen heterocycles with a broad spectrum of biological activities and, as such, are promising research targets. However, the potential roles of these compounds on bacterial resistance management remain to be better investigated. Therefore, the present study evaluated the antibacterial activity of 1,8-naphthyridine sulfonamides, addressing their ability to act as inhibitors of β-lactamases and efflux pump (QacA/B and QacC) against the strains SA-K4414 and SA-K4100 of <i>S. aureus</i>. All substances were prepared at an initial concentration of 1024 μg/mL, and their minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. Subsequently, their effects on β-lactamase- and efflux pump-mediated antibiotic resistance was evaluated from the reduction of the MIC of ethidium bromide (EtBr) and β-lactam antibiotics, respectively. The 1,8-naphthyridines did not present direct antibacterial activity against the strains SA-K4414 and SA-K4100 of <i>S. aureus</i>. On the other hand, when associated with antibiotics against both strains, the compounds reduced the MIC of EtBr and β-lactam antibiotics, suggesting that they may act by inhibiting β-lactamases and efflux pumps such as QacC and QacA/B. However, further research is required to elucidate the molecular mechanisms underlying these observed effects.https://www.mdpi.com/1420-3049/28/4/18191,8-naphthyridinesbacterial resistanceβ-lactamaseQacA/B efflux pumps<i>S. aureus</i> |
| spellingShingle | Cícera Datiane de Morais Oliveira-Tintino Saulo Relison Tintino Ana Carolina Justino de Araújo Cristina Rodrigues dos Santos Barbosa Priscilla Ramos Freitas José Bezerra de Araújo Neto Iêda Maria Begnini Ricardo Andrade Rebelo Luiz Everson da Silva Sandro Lucio Mireski Michele Caroline Nasato Maria Isabel Lacowicz Krautler Humberto Medeiros Barreto Jaime Ribeiro-Filho Irwin Rose Alencar de Menezes Henrique Douglas Melo Coutinho Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against <i>Staphylococcus aureus</i> Strains Molecules 1,8-naphthyridines bacterial resistance β-lactamase QacA/B efflux pumps <i>S. aureus</i> |
| title | Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against <i>Staphylococcus aureus</i> Strains |
| title_full | Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against <i>Staphylococcus aureus</i> Strains |
| title_fullStr | Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against <i>Staphylococcus aureus</i> Strains |
| title_full_unstemmed | Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against <i>Staphylococcus aureus</i> Strains |
| title_short | Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against <i>Staphylococcus aureus</i> Strains |
| title_sort | efflux pump qaca qacb and qacc and β lactamase inhibitors an evaluation of 1 8 naphthyridines against i staphylococcus aureus i strains |
| topic | 1,8-naphthyridines bacterial resistance β-lactamase QacA/B efflux pumps <i>S. aureus</i> |
| url | https://www.mdpi.com/1420-3049/28/4/1819 |
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