Baicalein exhibits inhibitory effect on the energy-dependent efflux pump activity in non-albicans Candidafungi

2014 â—½  
Vol 27 (1) â—½  
pp. 61-62 â—½  
Author(s):  
Paul Wai-Kei Tsang â—½  
Kwok-Yan Chau â—½  
Hai-Ping Yang
Keyword(s):  
Efflux Pump â—½  
Inhibitory Effect â—½  
Pump Activity â—½  
Energy Dependent

scholarly journals New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action

Antibiotics â—½  
2021 â—½  
Vol 10 (6) â—½  
pp. 709
Author(s):  
Marta Jorba â—½  
Marina Pedrola â—½  
Ouldouz Ghashghaei â—½  
Rocío Herráez â—½  
Lluis Campos-Vicens â—½  
...  
Keyword(s):  
Inhibitory Concentration â—½  
Efflux Pump â—½  
Synergistic Effects â—½  
Nicotinamide Adenine Dinucleotide Phosphate â—½  
Detailed Characterization â—½  
Low Concentrations â—½  
Pump Activity â—½  
Bacteriological Evaluation â—½  
Kinetics Of

This work reports a detailed characterization of the antimicrobial profile of two trimethoprim-like molecules (compounds 1a and 1b) identified in previous studies. Both molecules displayed remarkable antimicrobial activity, particularly when combined with sulfamethoxazole. In disk diffusion assays on Petri dishes, compounds 1a and 1b showed synergistic effects with colistin. Specifically, in combinations with low concentrations of colistin, very large increases in the activities of compounds 1a and 1b were determined, as demonstrated by alterations in the kinetics of bacterial growth despite only slight changes in the fractional inhibitory concentration index. The effect of colistin may be to increase the rate of antibiotic entry while reducing efflux pump activity. Compounds 1a and 1b were susceptible to extrusion by efflux pumps, whereas the inhibitor phenylalanine arginyl β-naphthylamide (PAβN) exerted effects similar to those of colistin. The interactions between the target enzyme (dihydrofolate reductase), the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH), and the studied molecules were explored using enzymology tools and computational chemistry. A model based on docking results is reported.

scholarly journals The TonB system in Aeromonas hydrophila NJ-35 is essential for MacA2B2 efflux pump-mediated macrolide resistance

Veterinary Research â—½  
2021 â—½  
Vol 52 (1) â—½  
Author(s):  
Yuhao Dong â—½  
Qing Li â—½  
Jinzhu Geng â—½  
Qing Cao â—½  
Dan Zhao â—½  
...  
Keyword(s):  
Aeromonas Hydrophila â—½  
Efflux Pump â—½  
Fold Increase â—½  
Activity Level â—½  
Macrolide Resistance â—½  
Wild Type â—½  
Iron Deprivation â—½  
Pump Activity â—½  
Tonb System â—½  
Increased Sensitivity

AbstractThe TonB system is generally considered as an energy transporting device for the absorption of nutrients. Our recent study showed that deletion of this system caused a significantly increased sensitivity of Aeromonas hydrophila to the macrolides erythromycin and roxithromycin, but had no effect on other classes of antibiotics. In this study, we found the sensitivity of ΔtonB123 to all macrolides tested revealed a 8- to 16-fold increase compared with the wild-type (WT) strain, but this increase was not related with iron deprivation caused by tonB123 deletion. Further study demonstrated that the deletion of tonB123 did not damage the integrity of the bacterial membrane but did hinder the function of macrolide efflux. Compared with the WT strain, deletion of macA2B2, one of two ATP-binding cassette (ABC) types of the macrolide efflux pump, enhanced the sensitivity to the same levels as those of ΔtonB123. Interestingly, the deletion of macA2B2 in the ΔtonB123 mutant did not cause further increase in sensitivity to macrolide resistance, indicating that the macrolide resistance afforded by the MacA2B2 pump was completely abrogated by tonB123 deletion. In addition, macA2B2 expression was not altered in the ΔtonB123 mutant, indicating that any influence of TonB on MacA2B2-mediated macrolide resistance was at the pump activity level. In conclusion, inactivation of the TonB system significantly compromises the resistance of A. hydrophila to macrolides, and the mechanism of action is related to the function of MacA2B2-mediated macrolide efflux.

Azole resistance inCandida albicansfrom animals: Highlights on efflux pump activity and gene overexpression

Mycoses â—½  
10.1111/myc.12611 â—½  
2017 â—½  
Vol 60 (7) â—½  
pp. 462-468 â—½  
Author(s):  
Marcos Fábio Gadelha Rocha â—½  
Silviane Praciano Bandeira â—½  
Lucas Pereira de Alencar â—½  
Luciana Magalhães Melo â—½  
Jamille Alencar Sales â—½  
...  
Keyword(s):  
Efflux Pump â—½  
Gene Overexpression â—½  
Azole Resistance â—½  
Pump Activity

Amino Acid Transport in a Water-mould: The Possible Regulatory Roles of Calcium and N6-(Δ2-isopentenyl)adenine

10.1139/o75-134 â—½  
1975 â—½  
Vol 53 (9) â—½  
pp. 975-988 â—½  
Author(s):  
Danny P. Singh â—½  
Hérb. B. LéJohn
Keyword(s):  
Amino Acids â—½  
Amino Acid â—½  
Amino Acid Transport â—½  
Osmotic Shock â—½  
Inhibitory Effect â—½  
Transport Systems â—½  
Acid Transport â—½  
Isopentenyl Adenine â—½  
Energy Dependent â—½  
Water Mould

Transport of amino acids in the water-mould Achlya is an energy-dependent process. Based on competition kinetics and studies involving the influence of pH and temperature on the initial transport rates, it was concluded that the 20 amino acids (L-isomers) commonly found in proteins were transported by more than one, possibly nine, uptake systems. This is similar to the pattern elucidated for some bacteria but unlike those uncovered for all fungi studied to date. The nine different transport systems elucidated are: (i) methionine, (ii) cysteine, (iii) proline, (iv) serine–threonine, (v) aspartic and glutamic acids, (vi) glutamine and asparagine, (vii) glycine and alanine, (viii) histidine, lysine, and arginine, and (ix) phenylalanine–tyrosine–tryptophan and leucine–isoleucine–valine as two overlapping groups. Transport of all of these amino acids was inhibited by azide, cyanide, and its derivatives and 2,4-dinitrophenol. These agents normally interfere with metabolism at the level of the electron transport chain and oxidative phosphorylation. Osmotic shock treatment of the cells released, into the shock fluid, a glycopeptide that binds calcium as well as tryptophan but no other amino acid. The shocked cells are incapable of concentrating amino acids, but remain viable and reacquire this capacity when the glycopeptide is resynthesized.Calcium played more than a secondary role in the transport of the amino acids. When bound to the membrane-localized glycopeptide, it permits concentrative transport to take place. However, excess calcium can inhibit transport which can be overcome by chelating with citrate. Calculations show that the concentration of free citrate is most important. At low citrate concentrations (less than 1 mM) in the absence of exogenously supplied calcium, enhancement of amino acid transport occurs. At high concentrations (greater than 5 mM), citrate inhibits but this effect can be reversed by titrating with calcium. Evidently, the glycopeptide acts as a calcium sink to regulate the concentration of calcium made available to the cell for its membrane activities.N6-(Δ2-isopentenyl) adenine (a plant growth 'hormone') and analogues mimic the inhibitory effect of citrate and bind to the glycopeptide as well. Replot data for citrate and N6-(Δ2-isopentyl) adenine inhibition indicate that both agents have no more than one binding constant. These results implicate calcium, glycopeptide, and energy-dependent transport of solutes in some, as yet undefinable, way.

scholarly journals Effect of Bile on the Cell Surface Permeability Barrier and Efflux System of Vibrio cholerae

2004 â—½  
Vol 186 (20) â—½  
pp. 6809-6814 â—½  
Author(s):  
Arpita Chatterjee â—½  
Sohini Chaudhuri â—½  
Gargi Saha â—½  
Satadeepa Gupta â—½  
Rukhsana Chowdhury
Keyword(s):  
Outer Membrane â—½  
Vibrio Cholerae â—½  
Efflux Pump â—½  
Permeability Barrier â—½  
Synergistic Activity â—½  
Efflux System â—½  
Gram Negative â—½  
Outer Leaflet â—½  
Hydrophobic Compounds â—½  
Energy Dependent

ABSTRACT Gram-negative bacteria are inherently impermeable to hydrophobic compounds, due to the synergistic activity of the permeability barrier imposed by the outer membrane and energy dependent efflux systems. The gram-negative, enteric pathogen Vibrio cholerae appears to be deficient in both these activities; the outer membrane is not an effective barrier to hydrophobic permeants, presumably due to the presence of exposed phospholipids on the outer leaflet of the outer membrane, and efflux systems are at best only partially active. When V. cholerae was grown in the presence of bile, entry of hydrophobic compounds into the cells was significantly reduced. No difference was detected in the extent of exposed phospholipids on the outer leaflet of the outer membrane between cells grown in the presence or absence of bile. However, in the presence of energy uncouplers, uptake of hydrophobic probes was comparable between cells grown in the presence or absence of bile, indicating that energy-dependent efflux processes may be involved in restricting the entry of hydrophobic permeants into bile grown cells. Indeed, an efflux system(s) is essential for survival of V. cholerae in the presence of bile. Expression of acrAB, encoding an RND family efflux pump, was significantly increased in V. cholerae cells grown in vitro in the presence of bile and also in cells grown in rabbit intestine.

scholarly journals A Combination Fluorescence Assay Demonstrates Increased Efflux Pump Activity as a Resistance Mechanism in Azole-Resistant Vaginal Candida albicans Isolates

2016 â—½  
Vol 60 (10) â—½  
pp. 5858-5866 â—½  
Author(s):  
Somanon Bhattacharya â—½  
Jack D. Sobel â—½  
Theodore C. White
Keyword(s):  
Candida Albicans â—½  
Efflux Pump â—½  
Pathogenic Fungus â—½  
Resistance Mechanism â—½  
Efflux Pumps â—½  
Resistant Isolate â—½  
Vaginal Infections â—½  
Content Type â—½  
Qrt Pcr â—½  
Pump Activity

ABSTRACTCandida albicansis a pathogenic fungus causing vulvovaginal candidiasis (VVC). Azole drugs, such as fluconazole, are the most common treatment for these infections. Recently, azole-resistant vaginalC. albicansisolates have been detected in patients with recurring and refractory vaginal infections. However, the mechanisms of resistance in vaginalC. albicansisolates have not been studied in detail. In oral and systemic resistant isolates, overexpression of the ABC transporters Cdr1p and Cdr2p and the major facilitator transporter Mdr1p is associated with resistance. Sixteen fluconazole-susceptible and 22 fluconazole-resistant vaginalC. albicansisolates were obtained, including six matched sets containing a susceptible and a resistant isolate, from individual patients. Using quantitative real-time reverse transcriptase PCR (qRT-PCR), 16 of 22 resistant isolates showed overexpression of at least one efflux pump gene, while only 1 of 16 susceptible isolates showed such overexpression. To evaluate the pump activity associated with overexpression, an assay that combined data from two separate fluorescent assays using rhodamine 6G and alanine β-naphthylamide was developed. The qRT-PCR results and activity assay results were in good agreement. This combination of two fluorescent assays can be used to study efflux pumps as resistance mechanisms in clinical isolates. These results demonstrate that efflux pumps are a significant resistance mechanism in vaginalC. albicansisolates.

scholarly journals Selective Inhibition of Coxiella burnetii Replication by the Steroid Hormone Progesterone

2020 â—½  
Vol 88 (12) â—½  
Author(s):  
Zachary P. Howard â—½  
Anders Omsland
Keyword(s):  
Coxiella Burnetii â—½  
Efflux Pump â—½  
Q Fever â—½  
Steroid Hormone â—½  
Natural Infection â—½  
Placental Tissue â—½  
Selective Inhibition â—½  
Inhibitory Effect â—½  
Content Type â—½  
Direct Inhibitory Effect

ABSTRACT Coxiella burnetii is a zoonotic bacterial obligate intracellular parasite and the cause of query (Q) fever. During natural infection of female animals, C. burnetii shows tropism for the placenta and is associated with late-term abortion, at which time the pathogen titer in placental tissue can exceed one billion bacteria per gram. During later stages of pregnancy, placental trophoblasts serve as the major source of progesterone, a steroid hormone known to affect the replication of some pathogens. During infection of placenta-derived JEG-3 cells, C. burnetii showed sensitivity to progesterone but not the immediate precursor pregnenolone or estrogen, another major mammalian steroid hormone. Using host cell-free culture, progesterone was determined to have a direct inhibitory effect on C. burnetii replication. Synergy between the inhibitory effect of progesterone and the efflux pump inhibitors verapamil and 1-(1-naphthylmethyl)-piperazine is consistent with a role for efflux pumps in preventing progesterone-mediated inhibition of C. burnetii activity. The sensitivity of C. burnetii to progesterone, but not structurally related molecules, is consistent with the ability of progesterone to influence pathogen replication in progesterone-producing tissues.

scholarly journals Dually Acting Nonclassical 1,4-Dihydropyridines Promote the Anti-Tuberculosis (Tb) Activities of Clofazimine

Molecules â—½  
2019 â—½  
Vol 24 (16) â—½  
pp. 2873 â—½  
Author(s):  
Fabian Lentz â—½  
Norbert Reiling â—½  
Gabriella Spengler â—½  
Annamária Kincses â—½  
Andrea Csonka â—½  
...  
Keyword(s):  
Efflux Pump â—½  
Substituent Effects â—½  
Drug Efficacy â—½  
Second Line â—½  
First Line â—½  
Resistance Development â—½  
Cell Line Model â—½  
Pump Activity â—½  
T Lymphoma â—½  
Poor Efficacy

The number of effective antituberculotic drugs is strongly limited to four first-line drugs in standard therapy. In case of resistances second-line antibiotics are used with a poor efficacy and tolerability. Therefore, novel antituberculotic drugs are urgently needed. We synthesized novel nonclassical 1,4-dihydropyridines and evaluated their antituberculotic properties depending on substituent effects. Preferred substituents could be identified. As related classical 1,4-dihydropyridines are known as inhibitors of the transmembrane efflux pump ABCB1 in cancer cells, we wondered whether a use of our compounds may be of favour to enhance the antituberculotic drug efficacy of the second-line antituberculotic drug clofazimine, which is a known substrate of ABCB1 by a suggested inhibition of a corresponding efflux pump in Mycobacterium tuberculosis (Mtb). For this, we determined the ABCB1 inhibiting properties of our compounds in a mouse T-lymphoma cell line model and then evaluated the drug-enhancing properties of selected compounds in a co-application with clofazimine in our Mtb strain. We identified novel enhancers of clofazimine toxicity which could prevent clofazimine resistance development mediated by an efflux pump activity.

scholarly journals Effects of 2-mercaptoacetate in isolated liver mitochondria in vitro. Competitive inhibition of 3-hydroxybutyrate dehydrogenase and depression of the β-oxidation pathway

Biochemical Journal â—½  
10.1042/bj2060053 â—½  
1982 â—½  
Vol 206 (1) â—½  
pp. 53-59 â—½  
Author(s):  
F Bauché â—½  
D Sabourault â—½  
Y Giudicelli â—½  
J Nordmann â—½  
R Nordmann
Keyword(s):  
Fatty Acid â—½  
Fatty Acid Oxidation â—½  
Competitive Inhibition â—½  
Liver Mitochondria â—½  
Inhibitory Effect â—½  
Acid Oxidation â—½  
Membrane Bound â—½  
Energy Dependent â—½  
Isolated Liver

The effects of 2-mercaptoacetate on the respiration rates induced by different substrates were studied in vitro in isolated liver mitochondria. With palmitoyl-L-carnitine or 2-oxoglutarate as the substrate, the ADP-stimulated respiration (State 3) was dose-dependently inhibited by 2-mercaptoacetate. with glutamate or succinate as the substrate. State-3 respiration was only slightly inhibited by 2-mercaptoacetate. In contrast, the oxidation rate of 3-hydroxybutyrate was competitively inhibited by 2-mercaptoacetate in both isolated mitochondria and submitochondrial particles. In uncoupled mitochondria and in mitochondria in which ATP- and GTP-dependent acyl-CoA biosynthesis was inhibited, the inhibitory effect of 2-mercaptoacetate on palmitoyl-L-carnitine oxidation was abolished; under the same conditions, however, inhibition of 3-hydroxybutyrate oxidation by 2-mercaptoacetate still persisted. These results led to the following conclusions: 2-mercaptoacetate itself enters the mitochondrial matrix, inhibits fatty acid oxidation through a mechanism requiring an energy-dependent activation of 2-mercaptoacetate and itself inhibits 3-hydroxybutyrate oxidation through a competitive inhibition of the membrane-bound 3-hydroxybutyrate dehydrogenase. This study also strongly suggests that the compound responsible for the inhibition of fatty acid oxidation is 2-mercaptoacetyl-CoA.

scholarly journals mmpL7 Gene of Mycobacterium tuberculosis Is Responsible for Isoniazid Efflux in Mycobacterium smegmatis

2005 â—½  
Vol 49 (11) â—½  
pp. 4775-4777 â—½  
Author(s):  
Maria R. Pasca â—½  
Paola Guglierame â—½  
Edda De Rossi â—½  
Francesca Zara â—½  
Giovanna Riccardi
Keyword(s):  
Mycobacterium Tuberculosis â—½  
High Resistance â—½  
Mycobacterium Smegmatis â—½  
Efflux Pump â—½  
Gene Encoding â—½  
Resistance Level â—½  
Carbonyl Cyanide â—½  
Resistance Nodulation Division â—½  
Efflux Pump Inhibitors â—½  
Energy Dependent

ABSTRACT The Mycobacterium tuberculosis mmpL7 gene, encoding a hypothetical resistance nodulation division transporter, confers a high resistance level to isoniazid when overexpressed in Mycobacterium smegmatis. The resistance level decreased in the presence of the efflux pump inhibitors reserpine and CCCP (carbonyl cyanide m-chlorophenylhydrazone). Energy-dependent efflux of isoniazid from M. smegmatis cells expressing the mmpL7 gene was observed.

Sign in / Sign up

Export Citation Format

Share Document