Tackling multidrug-resistant Staphylococcus aureus by natural products and their analogues acting as NorA efflux pump inhibitors

Kumar, Gaurav; Tudu, Asha Kiran

doi:10.1016/j.bmc.2023.117187

Cited by 13 publications

(8 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In in vitro studies performed with A. baumannii multiresistant strains showing efflux pump-mediated resistance, Riparin-B (Rip-B) was able to positively modulate norfloxacin’s effects [ 373 ]. Natural compounds have been also shown to be interesting inhibitors of the activity of efflux pumps with the aim of reducing the MIC of antimicrobial drugs [ 374 , 375 ]. Berberine (BBR), as a natural compound, has been, for example, proposed as an inhibitor of the MFS efflux pump MdfA in E. coli since it succeed in the significant increase in intracellular ciprofloxacin in resistant bacteria [ 376 ].…”

Section: Efflux Pumps Inhibitors: An Overviewmentioning

confidence: 99%

Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps

et al. 2023

View full text Add to dashboard Cite

The number of multidrug-resistant bacteria is rapidly spreading worldwide. Among the various mechanisms determining resistance to antimicrobial agents, multidrug efflux pumps play a noteworthy role because they export extraneous and noxious substrates from the inside to the outside environment of the bacterial cell contributing to multidrug resistance (MDR) and, consequently, to the failure of anti-infective therapies. The expression of multidrug efflux pumps can be under the control of transcriptional regulators and two-component systems (TCS). TCS are a major mechanism by which microorganisms sense and reply to external and/or intramembrane stimuli by coordinating the expression of genes involved not only in pathogenic pathways but also in antibiotic resistance. In this review, we describe the influence of TCS on multidrug efflux pump expression and activity in some Gram-negative and Gram-positive bacteria. Taking into account the strict correlation between TCS and multidrug efflux pumps, the development of drugs targeting TCS, alone or together with already discovered efflux pump inhibitors, may represent a beneficial strategy to contribute to the fight against growing antibiotic resistance.

show abstract

Section: Efflux Pumps Inhibitors: An Overviewmentioning

confidence: 99%

Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Products of natural origin are important sources in the search for molecules with antibacterial activities [23][24][25]. Furthermore, the combination of a natural compound with an antibiotic could potentialize the antibacterial activity and/or reduce the dose necessary for therapeutic success [24,26].…”

Section: Introductionmentioning

confidence: 99%

Chemical Composition, Antibacterial and Inhibitory Activity of the Efflux Pump of Essential Oils from Croton piauhiensis Müll.

Cruz,

de Freitas,

Costa

et al. 2023

Nutraceuticals

View full text Add to dashboard Cite

As the spread of bacterial resistance to clinically available antibiotics has become a global public health problem, the scientific community has intensified its studies in the search for natural compounds and their derivatives to combat bacterial resistance. In this work, a circadian study of the essential oil extracted from the leaves of Croton piauhiensis (EOCP) was carried out. We also sought to evaluate its antibacterial activity, modulatory potential and if it acts as a possible inhibitor of the efflux pump by determining the minimum inhibitory concentration (MIC) and the association of the oil in subinhibitory concentrations with the antibiotic ciprofloxacin and with ethidium bromide (EtBr) against the strain of Staphylococcus aureus K2068 strain. The assays used to obtain the MIC of the EOCP were performed by broth microdilution, while the efflux pump inhibitory test was performed by the MIC modification method. According to the results, the circadian study showed differences in the chemical composition and percentage of oils collected at different times of the day, which can be attributed to environmental conditions. The main components of the EOCP were β-caryophyllene (6 h—21.23%; 12 h—22.86% and 18 h—16.95%), followed by D-Limonene (6 h—13.27% and 18 h—15.95%) and γ-Elemene (12 h)—12.61%). The EOCP collected at 12 h had a better profile in reducing MIC, presenting antibacterial activity for Staphylococcus aureus and Escherichia coli. In the efflux pump test, it was observed that the oil was able to potentiate the action of ethidium bromide against the S. aureus K2068 strain, which can contribute to the prevention or treatment of infectious diseases caused by multidrug-resistant (MDR) strains.

show abstract

“…Given the impact of antibiotic resistance on public health (around 1.3 million deaths/year), the development of efflux pump inhibitors (EPIs) is one of the strategies used to combat bacteria resistant to multiple drugs (MDRs) [9,10]. The ability of EPIs to restore the effectiveness of existing antibiotics against MDR strains is even more prominent given the current context of the pharmaceutical industry, where investment in antibiotic research and development is decreasing despite the advancement of bacterial resistance [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Relevant in this context, the efflux pumps NorA and MepA are chro mosome-encoded transporters belonging to the major facilitator superfamily (MFS) an multidrug and toxic compound extrusion family (MATE), respectively [5,6]. These efflu pumps, in addition to having fluoroquinolones (e.g., norfloxacin and ciprofloxacin) a substrates, also extrude quaternary ammonium compounds (e.g., benzalkonium chlo ride), ethidium bromide (EtBr), pentamidine, acriflavine, and cetrimide, for example [7,8 Given the impact of antibiotic resistance on public health (around 1.3 millio deaths/year), the development of efflux pump inhibitors (EPIs) is one of the strategie used to combat bacteria resistant to multiple drugs (MDRs) [9,10]. The ability of EPIs t restore the effectiveness of existing antibiotics against MDR strains is even more promi nent given the current context of the pharmaceutical industry, where investment in anti biotic research and development is decreasing despite the advancement of bacterial re sistance [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus

Araújo-Neto,

Oliveira-Tintino,

de Araújo

et al. 2023

Antibiotics

View full text Add to dashboard Cite

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study’s objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus.

show abstract

Tackling multidrug-resistant Staphylococcus aureus by natural products and their analogues acting as NorA efflux pump inhibitors

Cited by 13 publications

References 143 publications

Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps

Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps

Chemical Composition, Antibacterial and Inhibitory Activity of the Efflux Pump of Essential Oils from Croton piauhiensis Müll.

3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus

Contact Info

Product

Resources

About