Effect of Carvacrol and Thymol on NorA efflux pump inhibition in multidrug-resistant (MDR) Staphylococcus aureus strains

2021 ◽  
Author(s):  
Cristina Rodrigues dos Santos Barbosa ◽  
Jackelyne Roberta Scherf ◽  
Thiago Sampaio de Freitas ◽  
Irwin Rose Alencar de Menezes ◽  
Raimundo Luiz Silva Pereira ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Efflux Pump Inhibition

scholarly journals Antibacterial Activity Against Multidrug-Resistant Staphylococcus aureus and in Silico Evaluation of MepA Efflux Pump by Cinnamaldehyde Chalcone

2021 ◽  
Vol 12 (6) ◽  
pp. 7523-7531
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Natural Products ◽  
Efflux Pump ◽  
Competitive Inhibitor ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Efflux Pump Inhibition ◽  
Phytochemical Studies

Phytochemical studies on Croton species have identified the presence of secondary metabolites responsible for a wide variety of pharmacological activities, among them antimicrobial activity. Research for new substances with antimicrobial activity derived from natural products can give a major contribution to human health worldwide by finding more efficient and fewer toxic formulas in the race against pathogenic microorganisms' resistance. Among bacterial pathogens, Staphylococcus aureus species, despite being present in the skin and nasal mucosa, can cause many infections and diseases. These opportunists reach debilitated people in hospitals and are challenging to treat. Here, we performed the structural characterization, determination of antibiotic activity, and MepA efflux pump inhibition potential against S. aureus of the chalcone (2E, 4E) -1- (2-hydroxy-3,4,6-trimethoxyphenyl)-5-phenylpenta-2,4-dien-1-one, derived from natural products 2-hydroxy-3,4,6-trimethoxyacetophenone isolated from Croton anisodontus and cinnamaldehyde. The chalcone was synthesized by the Claisen-Schmidt condensation. In addition, microbiological tests were performed to investigate the antibacterial activity, modulator potential, and efflux pump inhibition against the S. aureus multi-resistant strains. MIC values obtained to chalcone were not clinically relevant (MIC ≥ 1024 µg/mL). However, chalcone hampers the binding of the antibiotic to the binding site of the MepA efflux pump. It acts as a competitive inhibitor, being expelled from the bacteria in place of the antibiotic and potentiating ciprofloxacin's action against multidrug-resistant bacterial strains of K2068. Therefore, chalcone can be used as a base for substance design with antibiotic modifying activity.

Cocktail of CuO, ZnO, or CuZn Nanoparticles and Antibiotics for Combating Multidrug-Resistant Pseudomonas aeruginosa via Efflux Pump Inhibition

2021 ◽  
Vol 4 (9) ◽  
pp. 9799-9810
Author(s):  
Ioanna Eleftheriadou ◽  
Kleoniki Giannousi ◽  
Efthymia Protonotariou ◽  
Lemonia Skoura ◽  
Minas Arsenakis ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Efflux Pump Inhibition

scholarly journals Ethidium Bromide MIC Screening for Enhanced Efflux Pump Gene Expression or Efflux Activity in Staphylococcus aureus

2010 ◽  
Vol 54 (12) ◽  
pp. 5070-5073 ◽  
Author(s):  
Diixa Patel ◽  
Christos Kosmidis ◽  
Susan M. Seo ◽  
Glenn W. Kaatz
Keyword(s):  
Staphylococcus Aureus ◽  
Ethidium Bromide ◽  
Efflux Pump ◽  
Large Strain ◽  
Efflux Pumps ◽  
Multidrug Resistant ◽  
Reverse Transcription Pcr ◽  
Biocide Resistance ◽  
Straightforward Method ◽  
Short Period

ABSTRACT Multidrug resistance efflux pumps contribute to antimicrobial and biocide resistance in Staphylococcus aureus. The detection of strains capable of efflux is time-consuming and labor-intensive using currently available techniques. A simple and inexpensive method to identify such strains is needed. Ethidium bromide is a substrate for all but one of the characterized S. aureus multidrug-resistant (MDR) efflux pumps (NorC), leading us to examine the utility of simple broth microtiter MIC determinations using this compound in identifying efflux-proficient strains. Quantitative reverse transcription-PCR identified the increased expression of one or more MDR efflux pump genes in 151/309 clinical strains (49%). Ethidium bromide MIC testing was insensitive (48%) but specific (92%) in identifying strains with gene overexpression, but it was highly sensitive (95%) and specific (99%) in identifying strains capable of ethidium efflux. The increased expression of norA with or without other genes was most commonly associated with efflux, and in the majority of cases that efflux was inhibited by reserpine. Ethidium bromide MIC testing is a simple and straightforward method to identify effluxing strains and can provide accurate predictions of efflux prevalence in large strain sets in a short period of time.

scholarly journals First Isolation and Characterization of Chryseobacterium cucumeris SKNUCL01, Isolated from Diseased Pond loach (Misgurnus anguillicaudatus) in Korea

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 397
Author(s):  
Sang Guen Kim ◽  
Sib Giri ◽  
Sang Wha Kim ◽  
Jun Kwon ◽  
Sung Bin Lee ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Efflux Pump ◽  
Lethal Dose ◽  
Multidrug Resistant ◽  
Misgurnus Anguillicaudatus ◽  
Beta Lactamases ◽  
Isolation And Characterization ◽  
Efflux Pump Inhibition ◽  
Synergy Test

Loaches are widely distributed throughout the natural environment and are consumed for medicinal purposes in East Asia. Usually, loaches are cultured in ponds where the water conditions can easily cause bacterial infections. Infections due to bacterial pathogens such as Aeromonas have been well described in cultured loaches; however, there is no report regarding Chryseobacterium infection. This study focused on the elucidation of the pathogenic and antibiotic resistance characteristics of C. cucumeris, SKNUCL01, isolated from diseased loaches (Misgurnus anguillicaudatus). SKNUCL01 forms a biofilm, which is associated with its virulence. Koch’s postulates were satisfied with a lethal dose 50 (LD50) of 8.52 × 107 colony-forming units (CFU)/ml. Abrasion facilitates the mortality of the fish, which makes it a possible infection route for C. cucumeris. The strain showed resistance to nearly all tested antibiotics, such as trimethoprim/sulfamethoxazole, levofloxacin, and ciprofloxacin, formerly considered effective treatments. Phenotypic analyses for antibiotic resistance—the combined disk test, double-disk synergy test, modified Hodge test, and efflux pump inhibition test—revealed that the resistance of SKNUCL01 originated from metallo-beta lactamases (MBLs) and efflux pumps. Our findings provide evidence that could result in a breakthrough against multidrug-resistant Chryseobacterium infection in the aquaculture industry; the antibiotic resistance-related genes can be elucidated through future study.

An Update on Staphylococcus aureus NorA Efflux Pump Inhibitors

2020 ◽  
Vol 20 (24) ◽  
pp. 2168-2185
Author(s):  
Kadja Luana Chagas Monteiro ◽  
Thiago Mendonça de Aquino ◽  
Francisco Jaime B. Mendonça Junior
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Resistance ◽  
Efflux Pump ◽  
Control Strategies ◽  
Structural Diversity ◽  
Multidrug Resistant ◽  
Efflux Pump Inhibitors ◽  
Vancomycin Resistant ◽  
Sulfur Containing ◽  
Substantial Degree

Background: Methicillin-resistant and vancomycin-resistant Staphylococcus aureus are pathogens causing severe infectious diseases that pose real public health threats problems worldwide. In S. aureus, the most efficient multidrug-resistant system is the NorA efflux pump. For this reason, it is critical to identify efflux pump inhibitors. Objective: In this paper, we present an update of the new natural and synthetic compounds that act as modulators of antibiotic resistance through the inhibition of the S. aureus NorA efflux pump. Results: Several classes of compounds capable of restoring the antibiotic activity have been identified against resistant-S. aureus strains, acting as NorA efflux pump inhibitors. The most promising classes of compounds were quinolines, indoles, pyridines, phenols, and sulfur-containing heterocycles. However, the substantial degree structural diversity of these compounds makes it difficult to establish good structure- activity correlations that allow the design of compounds with more promising activities and properties. Conclusion: Despite substantial efforts put forth in the search for new antibiotic adjuvants that act as efflux pump inhibitors, and despite several promising results, there are currently no efflux pump inhibitors authorized for human or veterinary use, or in clinical trials. Unfortunately, it appears that infection control strategies have remained the same since the discovery of penicillin, and that most efforts remain focused on discovering new classes of antibiotics, rather than trying to prolong the life of available antibiotics, and simultaneously fighting mechanisms of bacterial resistance.

scholarly journals A novel mechanism of action of ketoconazole: inhibition of the NorA efflux pump system and biofilm formation in multidrug-resistant Staphylococcus aureus

2019 ◽  
Vol Volume 12 ◽  
pp. 1703-1718 ◽  
Author(s):  
Rehab M Abd El-Baky ◽  
Tim Sandle ◽  
James John ◽  
Gamal El-Din AA Abuo-Rahma ◽  
Helal F Hetta
Keyword(s):  
Staphylococcus Aureus ◽  
Mechanism Of Action ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Pump System

scholarly journals Microbe-Derived Indole Metabolite Demonstrates Potent Multidrug Efflux Pump Inhibition in Staphylococcus aureus

2019 ◽  
Vol 10 ◽  
Author(s):  
Rushikesh Tambat ◽  
Manoj Jangra ◽  
Nisha Mahey ◽  
Nishtha Chandal ◽  
Manpreet Kaur ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Efflux Pump ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Efflux Pump Inhibition

scholarly journals Dihydrostilbenes from Indigofera Pulchra

2008 ◽  
Vol 3 (5) ◽  
pp. 1934578X0800300
Author(s):  
Aliyu Musa ◽  
A. K. Haruna ◽  
M. Ilyas ◽  
Augustine Ahmadu ◽  
Simon Gibbons ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Nmr Spectroscopy ◽  
Structure Elucidation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Efflux Pump ◽  
2D Nmr ◽  
Multidrug Resistant ◽  
Methicillin Resistant ◽  
Weak Activity

A mixture of two new dihydrostilbenes, 3-methoxy-4,5-methylenedioxy-4′- O-(2ξ,3-dihydroxy-3-methylbutyl)-dihydrostilbene (1) and 3,5-dimethoxy-4′- O-(2ξ,3-dihydroxy-3-methylbutyl)-dihydrostilbene (2), was isolated from Indigofera pulchra as an inseparable mixture. Several isolation strategies, including multiple preparative TLC, SPE and finally HPLC were undertaken in an attempt to separate these metabolites, but to no avail. Structure elucidation on the mixture was conducted and we were able to establish the structures of these compounds unambiguously by MS and a series of 1D and 2D-NMR analyses. The mixture of these dihydrostilbenes was analyzed by NMR spectroscopy and 1 and 2 were in a ratio of 52:48, respectively, and this was evaluated against a panel of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant variants of this organism, including a strain over-expressing the NorA efflux pump; weak activity was observed.

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