scholarly journals Efflux Pump Inhibition and Resistance Modulation in Mycobacterium smegmatis by Peucedanum ostruthium and Its Coumarins

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1075
Author(s):  
Katarina Šimunović ◽  
Julia Solnier ◽  
Fabian Alperth ◽  
Olaf Kunert ◽  
Sonja Smole Smole Možina ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Smegmatis ◽  
Antibacterial Effect ◽  
Efflux Pump ◽  
Antimicrobial Effect ◽  
Drug Resistant ◽  
Health Crisis ◽  
Efflux Pump Inhibition ◽  
Resistance Modulation ◽  
Distinct Role

Antibiotic resistance is a growing problem and may become the next major global health crisis if no timely actions are taken. Mycobacterial infections are widespread and, due to antibiotic resistance, also hard to treat and a major cause of mortality. Natural compounds have the potential to increase antibiotic effectiveness due to their resistance modulatory and antimicrobial effects. In this study, Peucedanum ostruthium extracts, fractions, and isolated compounds were investigated regarding their antimicrobial and resistance-modulatory effects as well as efflux pump inhibition in Mycobacterium smegmatis. P. ostruthium extracts were found to have anti-mycobacterial potential and resistance modulating effects on ethidium bromide activity. The major antibacterial effect was attributed to ostruthin, and we found that the more lipophilic the substrate, the greater the antimicrobial effect. Imperatorin caused potent modulatory effects by interfering with the action of the major LfrA efflux pump in M. smegmatis. The plant P. ostruthuim has a complex effect on M. smegmatis, including antibacterial, efflux pump inhibition, resistance modulation, and membrane permeabilization, and its major constituents, ostruthin and imperatorin, have a distinct role in these effects. This makes P. ostruthium and its coumarins promising therapeutics to consider in the fight against drug-resistant mycobacteria.

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.

scholarly journals Characterization of the Mycobacterial MSMEG-3762/63 Efflux Pump in Mycobacterium smegmatis Drug Efflux

2020 ◽  
Vol 11 ◽  
Author(s):  
Barbara De Siena ◽  
Nicoletta Campolattano ◽  
Gianluca D’Abrosca ◽  
Luigi Russo ◽  
Daire Cantillon ◽  
...  
Keyword(s):  
Mycobacterium Smegmatis ◽  
Nitrosative Stress ◽  
Efflux Pump ◽  
Drug Efflux ◽  
Drug Resistant ◽  
Antimicrobial Drugs ◽  
Bioinformatics Analyses ◽  
Major Health Problem ◽  
Mdr Tb ◽  
Biofilm Development

Multi-drug resistant tuberculosis (MDR-TB) represents a major health problem worldwide. Drug efflux and the activity of efflux transporters likely play important roles in the development of drug-tolerant and drug-resistant mycobacterial phenotypes. This study is focused on the action of a mycobacterial efflux pump as a mechanism of drug resistance. Previous studies demonstrated up-regulation of the TetR-like transcriptional regulator MSMEG_3765 in Mycobacterium smegmatis and its ortholog Rv1685c in Mycobacterium tuberculosis (Mtb) in acid-nitrosative stress conditions. MSMEG-3765 regulates the expression of the MSMEG_3762/63/65 operon, and of the orthologous region in Mtb (Rv1687c/86c/85c). MSMEG-3762 and Rv1687c are annotated as ATP-binding proteins, while MSMEG-3763 and Rv1686c are annotated as trans-membrane polypeptides, defining an ABC efflux pump in both M. smegmatis and Mtb. The two putative efflux systems share a high percentage of identity. To examine the role of the putative efflux system MSMEG-3762/63, we constructed and characterized a MSMEG-3763 deletion mutant in M. smegmatis (∆MSMEG_3763). By comparative analysis of wild type, knockout, and complemented strains, together with structural modeling and molecular docking bioinformatics analyses of the MSMEG-3763 trans-membrane protein, we define the protein complex MSMEG-3762/63 as an efflux pump. Moreover, we demonstrate involvement of this pump in biofilm development and in the extrusion of rifampicin and ciprofloxacin (CIP), antimicrobial drugs used in first- and second-line anti-TB therapies.

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

2018 ◽  
Vol 9 ◽  
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

scholarly journals The molecular basis of extensively drug-resistant Salmonella Typhi isolates from pediatric septicemia patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257744
Author(s):  
Chanmi Kim ◽  
Iqra Latif ◽  
Durga P. Neupane ◽  
Gi Young Lee ◽  
Ryan S. Kwon ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Typhoid Fever ◽  
Molecular Basis ◽  
Efflux Pump ◽  
Detection Methods ◽  
Fluoroquinolone Resistance ◽  
Medium Size ◽  
Drug Resistant ◽  
Pump System ◽  
Extensively Drug Resistant

Sepsis is a syndromic response to infections and is becoming an emerging threat to the public health sector, particularly in developing countries. Salmonella Typhi (S. Typhi), the cause of typhoid fever, is one primary cause of pediatric sepsis in typhoid endemic areas. Extensively drug-resistant (XDR) S. Typhi is more common among pediatric patients, which is responsible for over 90% of the reported XDR typhoid cases, but the majority of antibiotic resistance studies available have been carried out using S. Typhi isolates from adult patients. Here, we characterized antibiotic-resistance profiles of XDR S. Typhi isolates from a medium size cohort of pediatric typhoid patients (n = 45, 68.89% male and 31.11% female) and determined antibiotic-resistance-related gene signatures associated with common treatment options to typhoid fever patients of 18 XDR S. Typhi representing all 45 isolates. Their ages were 1–13 years old: toddlers aging 1–2 years old (n = 9, 20%), pre-schoolers aging 3–5 years old (n = 17, 37.78%), school-age children aging 6–12 years old (n = 17, 37.78%), and adolescents aging 13–18 years old (n = 2, 4.44%). Through analyzing blaTEM1, dhfR7, sul1, and catA1genes for multidrug-resistance, qnrS, gyrA, gyrB, parC, and parE for fluoroquinolone-resistance, blaCTX-M-15 for XDR, and macAB and acrAB efflux pump system-associated genes, we showed the phenotype of the XDR S. Typhi isolates matches with their genotypes featured by the acquisitions of the genes blaTEM1, dhfR7, sul1, catA1, qnrS, and blaCTX-M-15 and a point mutation on gyrA. This study informs the molecular basis of antibiotic-resistance among recent S. Typhi isolates from pediatric septicemia patients, therefore providing insights into the development of molecular detection methods and treatment strategies for XDR S. Typhi.

Comparative Drug Resistance Reversal Potential of Natural Glycosides: Potential of Synergy Niaziridin & Niazirin

2019 ◽  
Vol 19 (10) ◽  
pp. 847-860 ◽  
Author(s):  
Gaurav R. Dwivedi ◽  
Anupam Maurya ◽  
Dharmendra K. Yadav ◽  
Feroz Khan ◽  
Mahendra K. Gupta ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Expression Pattern ◽  
Moringa Oleifera ◽  
Efflux Pump ◽  
Reversal Potential ◽  
Drug Resistant ◽  
Reversal Agent ◽  
Efflux Pump Inhibition ◽  
In Silico Studies ◽  
Resistance Reversal

Background: Due to the limited availability of antibiotics, Gram-negative bacteria (GNB) acquire different levels of drug resistance. It raised an urgent need to identify such agents, which can reverse the phenomenon of drug resistance. Objective: To understand the mechanism of drug resistance reversal of glycosides; niaziridin and niazirin isolated from the pods of Moringa oleifera and ouabain (control) against the clinical isolates of multidrug-resistant Escherichia coli. Methods: The MICs were determined following the CLSI guidelines for broth micro-dilution. In-vitro combination studies were performed by broth checkerboard method followed by Time-Kill studies, the efflux pump inhibition assay, ATPase inhibitory activity, mutation prevention concentration and in-silico studies. Results: The results showed that both glycosides did not possess antibacterial activity of their own, but in combination, they reduced the MIC of tetracycline up to 16 folds. Both were found to inhibit efflux pumps, but niaziridin was the best. In real time expression pattern analysis, niaziridin was also found responsible for the down expression of the two important efflux pump acrB & yojI genes alone as well as in combination. Niaziridin was also able to over express the porin forming genes (ompA & ompX). These glycosides decreased the mutation prevention concentration of tetracycline. Conclusion: This is the first ever report on glycosides, niazirin and niaziridin acting as drug resistance reversal agent through efflux pump inhibition and modulation of expression pattern drug resistant genes. This study may be helpful in preparing an effective antibacterial combination against the drug-resistant GNB from a widely growing Moringa oleifera.

Insights into drug resistance mechanisms in Clostridium difficile

2017 ◽  
Vol 61 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Phurt Harnvoravongchai ◽  
Methinee Pipatthana ◽  
Surang Chankhamhaengdecha ◽  
Tavan Janvilisri
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Clostridium Difficile ◽  
Bacterial Infection ◽  
Efflux Pump ◽  
Primary Treatment ◽  
Resistance Mechanisms ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

The incidence of Clostridium difficile infection has been elevated and becoming common in hospitals worldwide. Although antibiotics usually serve as the primary treatment for bacterial infection including C. difficile infection, limitations and failures have been evident due to drug resistance. Antibiotic resistance in C. difficile has been recognized as one of the most important factors to promote the infection and increase the level of severity and the recurrence rate. Several outbreaks in many countries have been linked to the emergence of hypervirulent drug-resistant strains. This pathogen harbours various mechanisms against the actions of antibiotics. The present study highlights three main drug-resistant strategies in C. difficile including drug inactivation, target modification and efflux pump. Other mechanisms that potentially contribute to drug-resistant traits in this organism are also discussed.

scholarly journals A Simple Method for Assessment of MDR Bacteria for Over-Expressed Efflux Pumps

2013 ◽  
Vol 7 (1) ◽  
pp. 72-82 ◽  
Author(s):  
Marta Martins ◽  
Matthew P McCusker ◽  
Miguel Viveiros ◽  
Isabel Couto ◽  
Séamus Fanning ◽  
...  
Keyword(s):  
Ethidium Bromide ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Outer Cell ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Topoisomerase Iv ◽  
Simple Method ◽  
Gram Negative ◽  
Over Expression

It is known that bacteria showing a multi-drug resistance phenotype use several mechanisms to overcome the action of antibiotics. As a result, this phenotype can be a result of several mechanisms or a combination of thereof. The main mechanisms of antibiotic resistance are: mutations in target genes (such as DNA gyrase and topoisomerase IV); over-expression of efflux pumps; changes in the cell envelope; down regulation of membrane porins, and modified lipopolysaccharide component of the outer cell membrane (in the case of Gram-negative bacteria). In addition, adaptation to the environment, such as quorum sensing and biofilm formation can also contribute to bacterial persistence. Due to the rapid emergence and spread of bacterial isolates showing resistance to several classes of antibiotics, methods that can rapidly and efficiently identify isolates whose resistance is due to active efflux have been developed. However, there is still a need for faster and more accurate methodologies. Conventional methods that evaluate bacterial efflux pump activity in liquid systems are available. However, these methods usually use common efflux pump substrates, such as ethidium bromide or radioactive antibiotics and therefore, require specialized instrumentation, which is not available in all laboratories. In this review, we will report the results obtained with the Ethidium Bromide-agar Cartwheel method. This is an easy, instrument-free, agar based method that has been modified to afford the simultaneous evaluation of as many as twelve bacterial strains. Due to its simplicity it can be applied to large collections of bacteria to rapidly screen for multi-drug resistant isolates that show an over-expression of their efflux systems. The principle of the method is simple and relies on the ability of the bacteria to expel a fluorescent molecule that is substrate for most efflux pumps, ethidium bromide. In this approach, the higher the concentration of ethidium bromide required to produce fluorescence of the bacterial mass, the greater the efflux capacity of the bacterial cells. We have tested and applied this method to a large number of Gram-positive and Gram-negative bacteria to detect efflux activity among these multi-drug resistant isolates. The presumptive efflux activity detected by the Ethidium Bromide-agar Cartwheel method was subsequently confirmed by the determination of the minimum inhibitory concentration for several antibiotics in the presence and absence of known efflux pump inhibitors.

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
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