Enhancement of the antibiotic activity by quercetin against Staphylococcus aureus efflux pumps

Santos, Joycy Francely Sampaio dos; Tintino, Saulo Relison; Silva, Ana R.P. da; Barbosa, Cristina Rodrigues dos Santos; Scherf, Jackelyne Roberta; Silveira, Zildene de Sousa; Freitas, Thiago S.; Neto, Luiz Jardelino de Lacerda; Barros, Luiz Marivando; Menezes, Irwin Rose Alencar de; Coutinho, Henrique D.M.; Siqueira-Júnior, José P.; Cunha, Francisco Assis Bezerra da

doi:10.1007/s10863-021-09886-4

Cited by 22 publications

(20 citation statements)

References 54 publications

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“…Phenolic acids are part of a subgroup of phenolic compounds and are characterized by having a chemical structure consisting of a phenolic ring and a carboxylic acid organic function ( Kahkeshani et al, 2019 ). These compounds have been described as viable alternatives in reversing bacterial resistance mechanisms, such as efflux pumps ( dos Santos et al, 2021 ; Pinheiro et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of ellagic acid and gallic acid as efflux pump inhibitors in strains of Staphylococcus aureus

et al. 2022

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The Gram-positive bacterium Staphylococcus aureus is responsible for a number of infections and has been described to exhibit resistance to antibacterial drugs through different resistance mechanisms. Among these, active efflux has been shown to be one of the main mechanisms of bacterial resistance associated with S. aureus. In this sense, the aim of the present study was to evaluate the ability of the ellagic acid and gallic acid compounds to reverse resistance by inhibiting the efflux pumps present in S. aureus strains IS-58 and K2068 that express the TetK and MepA flux pumps, respectively. In addition, it was verified the toxicity of both compounds on Drosophila melanogaster. Broth microdilution assays were performed to obtain the MIC values of ellagic acid and gallic acid, while efflux pump inhibition was tested using a subinhibitory concentration of standard efflux pump inhibitors, gallic acid and ellagic acid (MIC/8), where the ability of these compounds to decrease the MIC of ethidium bromide (EtBr) and antibiotics was verified. Toxicity was evaluated by mortality and negative geotaxis assays in D. melanogaster. Ellagic acid and gallic acid showed no direct antibacterial activity on S. aureus strains carrying the efflux pumps TetK and MepA. However, when we look at the results for the TetK pump, we see that when the two acids were associated with the antibiotic tetracycline a potentiation of the antibacterial effect occurred, this behavior was also observed for the antibiotic ciprofloxacin in the MepA strain. For the efflux pump inhibition results, only the compound gallic acid showed potentiating effect on antibacterial activity when associated with the substrate EtBr for the IS-58 strain carrying the TetK efflux pump. Ellagic acid and gallic acid showed no toxicity on the model arthropod D. melanogaster. These results indicate the possible use of gallic acid as an adjuvant in antibiotic therapy against multidrug-resistant (MDR) bacteria.

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Section: Introductionmentioning

confidence: 99%

Evaluation of ellagic acid and gallic acid as efflux pump inhibitors in strains of Staphylococcus aureus

et al. 2022

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“…Verapamil is known to inhibit norA pumps but it is also a calcium channel blocker ( Holler et al, 2012 ). Natural compounds such as quercetin ( dos Santos et al, 2021 ), kaempferol rhamnoside, and reserpine showed potential inhibition of the norA efflux pump in SA ( Holler et al, 2012 ). In addition, efflux pump inhibition has been described in MRSA for kuwanon O isolated from M. alba ( Zhu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Prenylated phenolics from Morus alba against MRSA infections as a strategy for wound healing

et al. 2022

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Antimicrobial resistance is a public health threat and the increasing number of multidrug-resistant bacteria is a major concern worldwide. Common antibiotics are becoming ineffective for skin infections and wounds, making the search for new therapeutic options increasingly urgent. The present study aimed to investigate the antibacterial potential of prenylated phenolics in wound healing. Phenolic compounds isolated from the root bark of Morus alba L. were investigated for their antistaphylococcal potential both alone and in combination with commonly used antibiotics. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined by microdilution and agar method. Synergy was investigated using the checkerboard titration technique. Membrane-disrupting activity and efflux pump inhibition were evaluated to describe the potentiating effect. Prenylated phenolics inhibited bacterial growth of methicillin-resistant Staphylococcus aureus (MRSA) at lower concentrations (MIC 2–8 μg/ml) than commonly used antibiotics. The combination of active phenolics with kanamycin, oxacillin, and ciprofloxacin resulted in a decrease in the MIC of the antimicrobial agent. Kuwanon C, E, T, morusin, and albafuran C showed synergy (FICi 0.375–0.5) with oxacillin and/or kanamycin. Prenylated phenolics disrupted membrane permeability statistically significantly (from 28 ± 16.48% up to 73 ± 2.83%), and membrane disruption contributes to the complex antibacterial activity against MRSA. In addition, kuwanon C could be considered an efflux pump inhibitor. Despite the antibacterial effect on MRSA and the multiple biological activities, the prenylated phenolics at microbially significant concentrations have a minor effect on human keratinocyte (HaCaT) viability. In conclusion, prenylated phenolics in combination with commonly used antibiotics are promising candidates for the treatment of MRSA infections and wound healing, although further studies are needed.

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“…In other studies, the effectiveness of inhibiting the efflux pump mechanism was also demonstrated in Staphylococcus aureus strains by caffeic and gallic acid (the MrsA pumps of the strain RN-4220 and NorA of the strain 1199B) [73], hydroxyamines derived from lapachol and norlachol (NorA pumps from the strain 1199B) [74], ferulic acid and its esterified derivatives (NorA pumps from the strain 1199B) [75]. In contrast, studies [76] have shown the activity of blocking the efflux pump by quercetin. Quercetin showed synergism with all antibiotics tested.…”

Section: Antibacterial Activity Of the Habh And Cuhabh Complexesmentioning

confidence: 94%

From the Physicochemical Characteristic of Novel Hesperetin Hydrazone to Its In Vitro Antimicrobial Aspects

et al. 2022

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Microorganisms are able to give rise to biofilm formation on food matrixes and along food industry infrastructures or medical equipment. This growth may be reduced by the application of molecules preventing bacterial adhesion on these surfaces. A new Schiff base ligand, derivative of hesperetin, HABH (2-amino-N′-(2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene)benzohydrazide), and its copper complex, CuHABH [CuLH2(OAc)], were designed, synthesized and analyzed in terms of their structure and physicochemical properties, and tested as antibacterial agents. Their structures both in a solid state and in solution were established using several methods: FT-IR, 1H NMR, 13C NMR, UV-Vis, FAB MS, EPR, ESI-MS and potentiometry. Coordination binding of the copper(II) complex dominating at the physiological pH region in the solution was found to be the same as that detected in the solid state. Furthermore, the interaction between the HABH and CuHABH with calf-thymus DNA (CT-DNA) were investigated. These interactions were tracked by UV-Vis, CD (circular dichroism) and spectrofluorimetry. The results indicate a stronger interaction of the CuHABH with the CT-DNA than the HABH. It can be assumed that the nature of the interactions is of the intercalating type, but in the high concentration range, the complex can bind to the DNA externally to phosphate residues or to a minor/major groove. The prepared compounds possess antibacterial and antibiofilm activities against Gram-positive and Gram-negative bacteria. Their antagonistic activity depends on the factor-strain test system. The glass was selected as a model surface for the experiments on antibiofilm activity. The adhesion of bacterial cells to the glass surface in the presence of the compounds was traced by luminometry and the best antiadhesive action against both bacterial strains was detected for the CuHABH complex. This molecule may play a crucial role in disrupting exopolymers (DNA/proteins) in biofilm formation and can be used to prevent bacterial adhesion especially on glass equipment.

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Enhancement of the antibiotic activity by quercetin against Staphylococcus aureus efflux pumps

Cited by 22 publications

References 54 publications

Evaluation of ellagic acid and gallic acid as efflux pump inhibitors in strains of Staphylococcus aureus

Evaluation of ellagic acid and gallic acid as efflux pump inhibitors in strains of Staphylococcus aureus

Prenylated phenolics from Morus alba against MRSA infections as a strategy for wound healing

From the Physicochemical Characteristic of Novel Hesperetin Hydrazone to Its In Vitro Antimicrobial Aspects

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