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Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus
Khellin and visnagin are natural furanochromones that photoreact with DNA. Khellin has been used in the treatment of vitiligo and psoriasis, as well as in the treatment of angina pectoris and asthma due to its potent action as a coronary vasodilator and antispasmodic agent. The present study aimed t...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509268/ https://www.ncbi.nlm.nih.gov/pubmed/36164399 http://dx.doi.org/10.1155/2022/9244500 |
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author | Rodrigues, Damara F. Borges, Nathalie H. P. B. Nogueira, Carlos Emídio S. Tavares, Josean F. Arcanjo, Daniel Dias Rufino Barreto, Humberto M. Siqueira-Junior, José P. |
author_facet | Rodrigues, Damara F. Borges, Nathalie H. P. B. Nogueira, Carlos Emídio S. Tavares, Josean F. Arcanjo, Daniel Dias Rufino Barreto, Humberto M. Siqueira-Junior, José P. |
author_sort | Rodrigues, Damara F. |
collection | PubMed |
description | Khellin and visnagin are natural furanochromones that photoreact with DNA. Khellin has been used in the treatment of vitiligo and psoriasis, as well as in the treatment of angina pectoris and asthma due to its potent action as a coronary vasodilator and antispasmodic agent. The present study aimed to investigate whether the compounds khellin and visnagin act as inhibitors of NorA protein, an efflux pump overproduced by the strain of Staphylococcus aureus SA-1199B that confers resistance to the fluoroquinolones, such as norfloxacin and ciprofloxacin. These substances alone did not show antibacterial activity against the strain tested. On the other hand, when these compounds were added to the culture medium at subinhibitory concentration, they were able to reduce the minimum inhibitory concentration (MIC) of norfloxacin, ethidium bromide, as well as berberine, suggesting that these compounds are modulating agents of norfloxacin resistance, possibly due to NorA inhibition. Molecular docking analysis showed that both khellin and visnagin form hydrogen bonds with Arg310, an important residue in the interaction between NorA and its substrates, supporting the hypothesis that these compounds are NorA inhibitors. These results suggest a possible application of khellin and visnagin as adjuvants to norfloxacin in the treatment of infections caused by strains of S. aureus that overproduce NorA. |
format | Online Article Text |
id | pubmed-9509268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-95092682022-09-25 Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus Rodrigues, Damara F. Borges, Nathalie H. P. B. Nogueira, Carlos Emídio S. Tavares, Josean F. Arcanjo, Daniel Dias Rufino Barreto, Humberto M. Siqueira-Junior, José P. Evid Based Complement Alternat Med Research Article Khellin and visnagin are natural furanochromones that photoreact with DNA. Khellin has been used in the treatment of vitiligo and psoriasis, as well as in the treatment of angina pectoris and asthma due to its potent action as a coronary vasodilator and antispasmodic agent. The present study aimed to investigate whether the compounds khellin and visnagin act as inhibitors of NorA protein, an efflux pump overproduced by the strain of Staphylococcus aureus SA-1199B that confers resistance to the fluoroquinolones, such as norfloxacin and ciprofloxacin. These substances alone did not show antibacterial activity against the strain tested. On the other hand, when these compounds were added to the culture medium at subinhibitory concentration, they were able to reduce the minimum inhibitory concentration (MIC) of norfloxacin, ethidium bromide, as well as berberine, suggesting that these compounds are modulating agents of norfloxacin resistance, possibly due to NorA inhibition. Molecular docking analysis showed that both khellin and visnagin form hydrogen bonds with Arg310, an important residue in the interaction between NorA and its substrates, supporting the hypothesis that these compounds are NorA inhibitors. These results suggest a possible application of khellin and visnagin as adjuvants to norfloxacin in the treatment of infections caused by strains of S. aureus that overproduce NorA. Hindawi 2022-09-17 /pmc/articles/PMC9509268/ /pubmed/36164399 http://dx.doi.org/10.1155/2022/9244500 Text en Copyright © 2022 Damara F. Rodrigues et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Rodrigues, Damara F. Borges, Nathalie H. P. B. Nogueira, Carlos Emídio S. Tavares, Josean F. Arcanjo, Daniel Dias Rufino Barreto, Humberto M. Siqueira-Junior, José P. Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus |
title | Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus |
title_full | Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus |
title_fullStr | Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus |
title_full_unstemmed | Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus |
title_short | Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus |
title_sort | modulation of drug resistance by furanochromones in nora overexpressing staphylococcus aureus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509268/ https://www.ncbi.nlm.nih.gov/pubmed/36164399 http://dx.doi.org/10.1155/2022/9244500 |
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