Observation of efflux pump inhibition activity of naringenin, quercetin, and umbelliferone on some multidrug-resistant microorganisms

Objective: To study the efflux pump inhibition activity of Mucunacochinchinensis extracts Methods: Sensitivity assay was performed by Kirby Bauer technique. Effluxing ability of microbe was done by accretion, accumulation and efflux pump assays. Results: Resistant fungal strains were subjected to efflux ability studies. Maximum effluxing ability was determined from the experimental data and it was found to be 105 min and 75 min by Candida albicans for methanolic extract of M. cochinchinenesis (MMC) and ethanolic extract of M. cochinchinensis (EMC) respectively and 45 min and 105 min by Aspergillus niger for MMC and EMC respectively. Profound synergistic effect of inhibition was observed with combined MMC and standard Clotrimoxazole when compared to the standard alone; against C. albicansindicates the modulating efficacy of MMC. Conclusion: M. cochinchinensis extracts showed efflux pump modulating activity.

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Efflux Pump Inhibition Effect of Curcumin and Phenylalanine Arginyl β- Naphthylamide (PAβN) against Multidrug Resistant Pseudomonas Aeruginosa Isolated from Burn Infections in Tanta University Hospitals

The Egyptian Journal of Medical Microbiology ◽

10.12816/0046279 ◽

2017 ◽

Vol 26 (1) ◽

pp. 113-119 ◽

Cited By ~ 3

Author(s):

Kareman Ahmed Eshra ◽

Marwa Mostafa Shalaby

Keyword(s):

Pseudomonas Aeruginosa ◽

Efflux Pump ◽

Multidrug Resistant ◽

University Hospitals ◽

Inhibition Effect ◽

Efflux Pump Inhibition

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

Pathogens ◽

10.3390/pathogens9050397 ◽

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.

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Identification of a Novel Polyamine Scaffold With Potent Efflux Pump Inhibition Activity Toward Multi-Drug Resistant Bacterial Pathogens

Frontiers in Microbiology ◽

10.3389/fmicb.2018.01301 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 6

Author(s):

Renee M. Fleeman ◽

Ginamarie Debevec ◽

Kirsten Antonen ◽

Jessie L. Adams ◽

Radleigh G. Santos ◽

...

Keyword(s):

Efflux Pump ◽

Bacterial Pathogens ◽

Drug Resistant ◽

Inhibition Activity ◽

Efflux Pump Inhibition

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

Biointerface Research in Applied Chemistry ◽

10.33263/briac126.75237531 ◽

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.

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The “racemic approach” in the evaluation of the enantiomeric NorA efflux pump inhibition activity of 2-phenylquinoline derivatives

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2016.07.003 ◽

2016 ◽

Vol 129 ◽

pp. 182-189 ◽

Cited By ~ 8

Author(s):

Andrea Carotti ◽

Federica Ianni ◽

Stefano Sabatini ◽

Alessandro Di Michele ◽

Roccaldo Sardella ◽

...

Keyword(s):

Efflux Pump ◽

Inhibition Activity ◽

Efflux Pump Inhibition

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Characteristics of Quinolone Resistance in Multidrug-resistant Acinetobacter baumannii Strains Isolated from General Hospitals

Jundishapur Journal of Microbiology ◽

10.5812/jjm.115128 ◽

2021 ◽

Vol 14 (3) ◽

Author(s):

Choong Ki Hong ◽

Joon Kim ◽

Ga-Yeon Kim

Keyword(s):

Acinetobacter Baumannii ◽

Antimicrobial Susceptibility ◽

Multilocus Sequence Typing ◽

Efflux Pump ◽

Multidrug Resistant ◽

Quinolone Resistance ◽

Efflux Pump Inhibitor ◽

General Hospitals ◽

Flight Mass Spectrometry ◽

Efflux Pump Inhibition

Background: Acinetobacter baumannii is the causative agent in various types of hospital-acquired infections, including respiratory, urinary tract, and wound infections. Objectives: This study investigated the primary mechanisms underlying quinolone resistance in A. baumannii strains, isolated from samples collected from general hospitals. Methods: Ninety-eight strains of A. baumannii were isolated from clinical specimens from general hospitals from 2017 – 2019. Antimicrobial susceptibility, efflux pump inhibition tests, multilocus sequence typing (MLST), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analyses were conducted on 64 strains, and the blaoxa-51-like gene sequence was detected. Results: In the antimicrobial susceptibility test, 78.1% (n = 50) of the strains exhibited resistance to ciprofloxacin, a quinolone antibiotic, and 57.8% (n = 37) strains were multidrug resistant (MDR). For 18 strains, the minimum inhibitory concentration of ciprofloxacin reduced in presence of an efflux pump inhibitor. Sequence analysis revealed that in 50 strains of A. baumannii, the codon for serine (TCA) in gyrA was replaced by that for leucine (TTA), whereas in 43 strains, the codon for serine (TCG) in parC was replaced by that for leucine (TTG). Multilocus sequence typing analysis confirmed 18 sequence types, and allelic number analysis showed the presence of nine gyrB alleles, with gyrB3 showing the highest frequency (62.5%). Conclusions: The findings of this study will be useful in improving treatment efficiency and preventing the spread of A. baumannii (both MDR and non-MDR strains).

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In Vitro Synergy of Ciprofloxacin and Gatifloxacin against Ciprofloxacin-Resistant Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.7.2959-2964.2005 ◽

2005 ◽

Vol 49 (7) ◽

pp. 2959-2964 ◽

Cited By ~ 51

Author(s):

George A. Pankey ◽

Deborah S. Ashcraft

Keyword(s):

Pseudomonas Aeruginosa ◽

Efflux Pump ◽

In Vitro Study ◽

Multidrug Resistant ◽

Efflux Pump Inhibition ◽

Pump Mechanism ◽

Time Kill ◽

Synergy Testing ◽

Unique Plasmid

ABSTRACT Multidrug-resistant Pseudomonas aeruginosa with combined decreased susceptibility to ceftazidime, ciprofloxacin, imipenem, and piperacillin is increasingly being found as a cause of nosocomial infections. It is important to look for combinations of drugs that might be synergistic. Ciprofloxacin resistance by P. aeruginosa is mediated in part by an efflux pump mechanism. Gatifloxacin, an 8-methoxyfluoroquinolone, inhibits a staphylococcal efflux pump. An earlier in vitro study using an Etest synergy method and time-kill assay suggested synergy of ciprofloxacin and gatifloxacin against P. aeruginosa. Synergy testing was performed by Etest and time-kill assay for 31 clinically unique, plasmid DNA distinct, U.S. P. aeruginosa isolates. Etest MICs for ciprofloxacin were 4 to >32 μg/ml, and for gatifloxacin they were >32 μg/ml. Ciprofloxacin plus gatifloxacin showed synergy by the Etest method for 6 (19%) of the 31 P. aeruginosa isolates using a summation fractional inhibitory concentration of ≤0.5 for synergy. Synergy was demonstrated for 13/31 (42%) of isolates by time-kill assay. No antagonism was detected. The remaining isolates were indifferent to the combination. The Etest method and time-kill assay were 65% (20/31) concordant. The mechanism of the in vitro synergy may include P. aeruginosa ciprofloxacin efflux pump inhibition by gatifloxacin.

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Substitutions in SurA and BamA Lead to Reduced Susceptibility to Broad Range Antibiotics in Gonococci

Genes ◽

10.3390/genes12091312 ◽

2021 ◽

Vol 12 (9) ◽

pp. 1312

Author(s):

Ivan Bodoev ◽

Maja Malakhova ◽

Julia Bespyatykh ◽

Dmitry Bespiatykh ◽

Georgij Arapidi ◽

...

Keyword(s):

Clinical Isolate ◽

Efflux Pump ◽

Cell Envelope ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Antibiotic Resistant ◽

Efflux Pump Inhibition ◽

Periplasmic Chaperone ◽

Quantitative Changes ◽

Periplasmic Chaperones

There is growing concern about the emergence and spread of multidrug-resistant Neisseria gonorrhoeae. To effectively control antibiotic-resistant bacterial pathogens, it is necessary to develop new antimicrobials and to understand the resistance mechanisms to existing antibiotics. In this study, we discovered the unexpected onset of drug resistance in N. gonorrhoeae caused by amino acid substitutions in the periplasmic chaperone SurA and the β-barrel assembly machinery component BamA. Here, we investigated the i19.05 clinical isolate with mutations in corresponding genes along with reduced susceptibility to penicillin, tetracycline, and azithromycin. The mutant strain NG05 (surAmut bamAmut, and penAmut) was obtained using the pan-susceptible n01.08 clinical isolate as a recipient in the transformation procedure. Comparative proteomic analysis of NG05 and n01.08 strains revealed significantly increased levels of other chaperones, Skp and FkpA, and some transport proteins. Efflux pump inhibition experiments demonstrated that the reduction in sensitivity was achieved due to the activity of efflux pumps. We hypothesize that the described mutations in the surA and bamA genes cause the qualitative and quantitative changes of periplasmic chaperones, which in turn alters the function of synthesized cell envelope proteins.

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