Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1784895715144630272
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
work_keys_str_mv AT oliveiratintinociceradatianedemorais effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT tintinosaulorelison effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT justinodearaujoanacarolina effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT dossantosbarbosacristinarodrigues effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT ramosfreitaspriscilla effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT dearaujonetojosebezerra effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT begniniiedamaria effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT rebeloricardoandrade effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT dasilvaluizeverson effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT mireskisandrolucio effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT nasatomichelecaroline effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT krautlermariaisabellacowicz effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT barretohumbertomedeiros effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT ribeirofilhojaime effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT demenezesirwinrosealencar effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains
AT coutinhohenriquedouglasmelo effluxpumpqacaqacbandqaccandblactamaseinhibitorsanevaluationof18naphthyridinesagainststaphylococcusaureusstrains