Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus .

Autor: Rodrigues DF; Laboratory of Genetics of Microorganisms, Department of Molecular Biology, Federal University of Paraiba, João Pessoa, PB, Brazil., Borges NHPB; Laboratory of Genetics of Microorganisms, Department of Molecular Biology, Federal University of Paraiba, João Pessoa, PB, Brazil., Nogueira CES; Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil., Tavares JF; Department Pharmaceutical Science, Federal University of Paraíba, João Pessoa, PB, Brazil., Arcanjo DDR; Laboratory of Functional and Molecular Studies on Physiopharmacology (LAFMOL), Department of Biophysics and Physiology, Federal University of Piauí, Teresina, PI, Brazil., Barreto HM; Laboratory of Research in Microbiology, Department of Parasitology and Microbiology, Federal University of Piaui, Teresina, PI, Brazil., Siqueira-Junior JP; Laboratory of Genetics of Microorganisms, Department of Molecular Biology, Federal University of Paraiba, João Pessoa, PB, Brazil.
Jazyk: angličtina
Zdroj: Evidence-based complementary and alternative medicine : eCAM [Evid Based Complement Alternat Med] 2022 Sep 17; Vol. 2022, pp. 9244500. Date of Electronic Publication: 2022 Sep 17 (Print Publication: 2022).
DOI: 10.1155/2022/9244500
Abstrakt: 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.
Competing Interests: The authors declare that they have no conflicts of interest..
(Copyright © 2022 Damara F. Rodrigues et al.)
Databáze: MEDLINE
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