Evaluation of the tannic acid inhibitory effect against the NorA efflux pump of Staphylococcus aureus

Tintino, Saulo Relison; Oliveira-Tintino, Cícera Datiane Morais; Campina, Fábia F.; Silva, Raimundo L.P.; Costa, Maria do Socorro; Menezes, Irwin Rose Alencar de; Júnior, João Tavares Calixto; Siqueira-Júnior, José P.; Coutinho, Henrique Douglas Melo; Leal-Balbino, Tereza Cristina; Balbino, Valdir Queiroz

doi:10.1016/j.micpath.2016.04.003

Cited by 91 publications

(47 citation statements)

References 33 publications

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“…We show that this reduction in MICs is due to inhibition of carbapenemase activity in the CPE isolates, which was supported by enzymatic assay and computational simulation. This study also showed that TA does not act as an efflux pump inhibitor (EPI) in Enterobacteriaceae contrary to what was reported in A. baumannii and S. aureus (Chusri et al 2009; Tintino et al 2016).…”

Section: Introductioncontrasting

confidence: 72%

“…In this context, the use of adjuvants that inhibit efflux and hydrolysing enzymes of antibiotics are gaining widespread interest (Ayhan et al 2016; Sekyere & Amoako 2017). For instance, Chusri et al (Chusri et al 2009) and Tintino et al (Tintino et al 2016) showed that tannic acid (TA) a type of polyphenolic biomolecule which acts as an efflux-pump inhibitor (EPI) and potentiates the effects of several non-β-lactam antibiotics in Acinetobacter baumannii and Staphylococcus aureus , respectively. Payne et al also characterized series of tricyclic natural product- derived as potent large-spectrum MBL inhibitors (Payne et al 2002).…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Potentiation of Carbapenems with Tannic Acid Against Carbapenemase Producing Enterobacteriaceae: Exploring Natural Products as Potential Carbapenemase Inhibitors

Somboro

Sekyere

Amoako

et al. 2018

Preprint

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Resistance to antibiotics is increasing worldwide, necessitating urgent action to sustain the efficacy of existing antibiotics in clinical use. We show that tannic acid (TA) in combination with carbapenems can reduce and/or reverse the minimum inhibitory concentrations (MICs) of carbapenems to susceptible values in Enterobacteriaceae that express class A and B carbapenemases. MICs of carbapenems in the presence and absence of TA and other efflux pump inhibitors, TA-carbapenemases inhibition assays and computational studies were undertaken to determine the effect of TA on carbapenem susceptibility in Enterobacteriaceae. TA had the greatest effect on metallo-β-lactamases (MBLs) followed by class A serine-β-lactamases (SBLs). Antibiotic susceptibility testing showed that TA reversed the MICs of MBLs to susceptible values whilst substantially reducing the MICs of SBLs (class A). Tolerable cytotoxicity effect was observed for the concentrations tested. TA inhibited enzymes with a marked difference between ≈50% inhibition (IC50) for NDM-1 and KPC-2. Computational studies including molecular docking, molecular dynamics simulations and binding free energy calculations showed that TA interact with both MBLs and SBLs hydrophobic sites. Moreover, TA had a stronger binding affinity for MBLs than SBLs as the MBLs, specifically VIM-1 and NDM-1, interact with a larger number of their catalytic active-site residues than that of OXA- 48 and KPC-2. These in vitro evaluations together with computational simulation explain the potentiating effect of TA toward carbapenems against carbapenem-resistance enterobacteriaceae. This study proposes TA as a promising adjuvant for MBLs and SBLs.

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Section: Introductioncontrasting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

In Vitro Potentiation of Carbapenems with Tannic Acid Against Carbapenemase Producing Enterobacteriaceae: Exploring Natural Products as Potential Carbapenemase Inhibitors

Somboro

Sekyere

Amoako

et al. 2018

Preprint

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“…According to a study NorA efflux pump was found to be overexpressed in 43% of resistant strains of S. aureus ( Patel et al, 2010 ; Astolfi et al, 2017 ). NorA, an established multidrug efflux pump model in S. aureus , accounts for extruding quinolones, quaternary ammonium salts, acridines, rhodamines, verapamil, and ethidium bromide ( Kaatz et al, 2003 ; Khan et al, 2006 ; Leitner et al, 2011 ; Tegos et al, 2011 ; Holler et al, 2012 ; Schindler et al, 2013 ; Fontaine et al, 2015 ; Tintino et al, 2016 ). Recently some non-antibiotics derivatives as potent NorA efflux pump inhibitors have been reported utilizing pharmacophore based modeling and drug repurposing utilizing in silico approach ( Astolfi et al, 2017 ; Sabatini et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Boeravinone B, A Novel Dual Inhibitor of NorA Bacterial Efflux Pump of Staphylococcus aureus and Human P-Glycoprotein, Reduces the Biofilm Formation and Intracellular Invasion of Bacteria

et al. 2017

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This study elucidated the role of boeravinone B, a NorA multidrug efflux pump inhibitor, in biofilm inhibition. The effects of boeravinone B plus ciprofloxacin, a NorA substrate, were evaluated in NorA-overexpressing, wild-type, and knocked-out Staphylococcus aureus (SA-1199B, SA-1199, and SA-K1758, respectively). The mechanism of action was confirmed using the ethidium bromide accumulation and efflux assay. The role of boeravinone B as a human P-glycoprotein (P-gp) inhibitor was examined in the LS-180 (colon cancer) cell line. Moreover, its role in the inhibition of biofilm formation and intracellular invasion of S. aureus in macrophages was studied. Boeravinone B reduced the minimum inhibitory concentration (MIC) of ciprofloxacin against S. aureus and its methicillin-resistant strains; the effect was stronger in SA-1199B. Furthermore, time–kill kinetics revealed that boeravinone B plus ciprofloxacin, at subinhibitory concentration (0.25 × MIC), is as equipotent as that at the MIC level. This combination also had a reduced mutation prevention concentration. Boeravinone B reduced the efflux of ethidium bromide and increased the accumulation, thus strengthening the role as a NorA inhibitor. Biofilm formation was reduced by four–eightfold of the minimal biofilm inhibitory concentration of ciprofloxacin, effectively preventing bacterial entry into macrophages. Boeravinone B effectively inhibited P-gp with half maximal inhibitory concentration (IC50) of 64.85 μM. The study concluded that boeravinone B not only inhibits the NorA-mediated efflux of fluoroquinolones but also considerably inhibits the biofilm formation of S. aureus. Its P-gp inhibition activity demonstrates its potential as a bioavailability and bioefficacy enhancer.

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“…It has been shown [89][90][91][92] that the NorA efflux pumps are responsible for the decreasing of the concentration of some (hydrophilic) fluoroquinolone drugs in the bacterial cell and consequently for the loss of activity of these antibiotics in Staphylococcus aureus. According to the recent publication by Tintino et al [93], the tannic acid is an efficient inhibitor of the NorA efflux pumps in this bacterial strain. Thus, they showed that the administration of norfloxacin together with tannic acid (Fig.…”

Section: Fig 34 Azithromycin (A) and Erythromycin (B)mentioning

confidence: 81%

Fighting bacterial resistance: approaches, challenges, and opportunities in the search for new antibiotics.Part 1. Antibiotics used in clinical practice: mechanisms of action and the development of bacterial resistance

Zhivich

2017

Microbiology Independent Research Journal (MIR Journal)

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Hundreds of thousands of people are dying every year in the world from infections caused by drug resistant bacteria. Antibiotic resistance is a rapidly increasing problem mostly as a result of the worldwide overuse and misuse of antibiotics for conditions that do not require them. The rapid spread of antibiotic resistance in bacteria makes it necessary to intensify the development of new antibiotics and new methods to combat drug resistant bacteria. The goal of this publication is to review the approaches to finding new antibiotics that are active against drug resistant bacteria. The first part of this review is focused on an analysis of the mechanisms of action of antibiotics that are used in clinical practice as well as the mechanisms of bacterial resistance. The molecular structure and modes of action of these antibiotics are reviewed with examples of detailed mechanisms of drugs interaction with the targets in bacteria. General and specific mechanisms of bacterial resistance to these antibiotics are described. Examples of new antibiotics development active against the drug resistant bacteria are presented.

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Evaluation of the tannic acid inhibitory effect against the NorA efflux pump of Staphylococcus aureus

Cited by 91 publications

References 33 publications

In Vitro Potentiation of Carbapenems with Tannic Acid Against Carbapenemase Producing Enterobacteriaceae: Exploring Natural Products as Potential Carbapenemase Inhibitors

In Vitro Potentiation of Carbapenems with Tannic Acid Against Carbapenemase Producing Enterobacteriaceae: Exploring Natural Products as Potential Carbapenemase Inhibitors

Boeravinone B, A Novel Dual Inhibitor of NorA Bacterial Efflux Pump of Staphylococcus aureus and Human P-Glycoprotein, Reduces the Biofilm Formation and Intracellular Invasion of Bacteria

Fighting bacterial resistance: approaches, challenges, and opportunities in the search for new antibiotics.Part 1. Antibiotics used in clinical practice: mechanisms of action and the development of bacterial resistance

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