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Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains
The bacterial species Staphylococcus aureus 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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961278/ https://www.ncbi.nlm.nih.gov/pubmed/36838807 http://dx.doi.org/10.3390/molecules28041819 |
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author | Oliveira-Tintino, Cícera Datiane de Morais Tintino, Saulo Relison Justino de Araújo, Ana Carolina dos Santos Barbosa, Cristina Rodrigues Ramos Freitas, Priscilla de Araújo Neto, José Bezerra Begnini, Iêda Maria Rebelo, Ricardo Andrade da Silva, Luiz Everson Mireski, Sandro Lucio Nasato, Michele Caroline Krautler, Maria Isabel Lacowicz Barreto, Humberto Medeiros Ribeiro-Filho, Jaime de Menezes, Irwin Rose Alencar Coutinho, Henrique Douglas Melo |
author_facet | Oliveira-Tintino, Cícera Datiane de Morais Tintino, Saulo Relison Justino de Araújo, Ana Carolina dos Santos Barbosa, Cristina Rodrigues Ramos Freitas, Priscilla de Araújo Neto, José Bezerra Begnini, Iêda Maria Rebelo, Ricardo Andrade da Silva, Luiz Everson Mireski, Sandro Lucio Nasato, Michele Caroline Krautler, Maria Isabel Lacowicz Barreto, Humberto Medeiros Ribeiro-Filho, Jaime de Menezes, Irwin Rose Alencar Coutinho, Henrique Douglas Melo |
author_sort | Oliveira-Tintino, Cícera Datiane de Morais |
collection | PubMed |
description | The bacterial species Staphylococcus aureus 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 S. aureus. 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 S. aureus. 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. |
format | Online Article Text |
id | pubmed-9961278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99612782023-02-26 Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains Oliveira-Tintino, Cícera Datiane de Morais Tintino, Saulo Relison Justino de Araújo, Ana Carolina dos Santos Barbosa, Cristina Rodrigues Ramos Freitas, Priscilla de Araújo Neto, José Bezerra Begnini, Iêda Maria Rebelo, Ricardo Andrade da Silva, Luiz Everson Mireski, Sandro Lucio Nasato, Michele Caroline Krautler, Maria Isabel Lacowicz Barreto, Humberto Medeiros Ribeiro-Filho, Jaime de Menezes, Irwin Rose Alencar Coutinho, Henrique Douglas Melo Molecules Article The bacterial species Staphylococcus aureus 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 S. aureus. 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 S. aureus. 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. MDPI 2023-02-15 /pmc/articles/PMC9961278/ /pubmed/36838807 http://dx.doi.org/10.3390/molecules28041819 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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/). |
spellingShingle | Article Oliveira-Tintino, Cícera Datiane de Morais Tintino, Saulo Relison Justino de Araújo, Ana Carolina dos Santos Barbosa, Cristina Rodrigues Ramos Freitas, Priscilla de Araújo Neto, José Bezerra Begnini, Iêda Maria Rebelo, Ricardo Andrade da Silva, Luiz Everson Mireski, Sandro Lucio Nasato, Michele Caroline Krautler, Maria Isabel Lacowicz Barreto, Humberto Medeiros Ribeiro-Filho, Jaime de Menezes, Irwin Rose Alencar Coutinho, Henrique Douglas Melo Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains |
title | Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains |
title_full | Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains |
title_fullStr | Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains |
title_full_unstemmed | Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains |
title_short | Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines against Staphylococcus aureus Strains |
title_sort | efflux pump (qaca, qacb, and qacc) and β-lactamase inhibitors? an evaluation of 1,8-naphthyridines against staphylococcus aureus strains |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961278/ https://www.ncbi.nlm.nih.gov/pubmed/36838807 http://dx.doi.org/10.3390/molecules28041819 |
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