PubMed Journals Articles About "Bacterial Efflux Pump Inhibitors Pipeline Insights 2017 Updated" RSS

18:32 EDT 16th October 2018 | BioPortfolio

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Showing "Bacterial Efflux Pump Inhibitors Pipeline Insights 2017 Updated" PubMed Articles 1–25 of 14,000+

Efflux Pump Inhibitors, Alpha-Tocopherol and Aspirin: Role in Campylobacter jejuni and Campylobacter coli Fluoroquinolone Resistance.

This study aimed to investigate how efflux pump activity contributes to high fluoroquinolone (FQ) resistance in Campylobacter jejuni and Campylobacter coli isolates and to evaluate the modulatory effects of α-tocopherol and aspirin on FQ phenotypic resistance profiles. Minimum inhibitory concentration (MIC) values were obtained for different FQ agents following exposure to different efflux pump inhibitors (EPIs), including PaβN (50 μg/mL), which targets the cmeABC efflux system, and chlorpromazine (45...

Studies on 2-phenylquinoline Staphylococcus aureus NorA efflux pump inhibitors: New insights on the C-6 position.

The alarming and rapid spread of antimicrobial resistance among bacteria represents a high risk for global health. Targeting factors involved in resistance to restore the activity of failing antibiotics is a promising strategy to overcome this urgent medical need. Efflux pump inhibitors are able to increase antibiotic concentrations in bacteria, thus they can be considered true antimicrobial resistance breakers. In this work, continuing our studies on inhibitors of the Staphylococcus aureus NorA pump, we de...

Targeted Efflux Transporter Inhibitors - A Solution to Improve Poor Cellular Accumulation of Anti-Cancer Agents.

Efflux transporters function as vacuum cleaners of xenobiotics and therefore they hinder drugs to reach their targets at effective enough concentrations. Efflux pump inhibitors can be used to improve the cell accumulation of drugs, however all the current inhibitors lack selectivity towards cancer cells. L-Type amino acid transporter 1 (LAT1), which is expressed in many types of cancer cells can be utilized to target inhibitors of efflux transporters to these cells by converting the inhibitors into LAT1-uti...

A cell-based infection assay identifies efflux pump modulators that reduce bacterial intracellular load.

Bacterial efflux pumps transport small molecules from the cytoplasm or periplasm outside the cell. Efflux pump activity is typically increased in multi-drug resistant (MDR) pathogens; chemicals that inhibit efflux pumps may have potential for antibiotic development. Using an in-cell screen, we identified three efflux pump modulators (EPMs) from a drug diversity library. The screening platform uses macrophages infected with the human Gram-negative pathogen Salmonella enterica (Salmonella) to identify small m...

2-Phenylquinoline S. aureus NorA Efflux Pump Inhibitors: Evaluation of the Importance of Methoxy Groups Introduction.

Antimicrobial resistance (AMR) represents a hot topic in drug discovery. Besides the identification of new antibiotics, the use of non-antibiotic molecules to block resistance mechanisms is a powerful alternative. Bacterial efflux pumps exert an early step in AMR development by allowing bacteria to grow at sub-inhibitorial drug concentrations. Thus, efflux pump inhibitors (EPIs) offer a great opportunity to fight AMR. Given our experience in developing Staphylococcus aureus NorA EPIs, in this work, starting...

Quantifying the Evolutionary Conservation of Genes Encoding Multidrug Efflux Pumps in the ESKAPE Pathogens To Identify Antimicrobial Drug Targets.

Increasing rates of antibiotic-resistant bacterial infection are one of the most pressing contemporary global health concerns. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and species) have been identified as the leading global cause of multidrug-resistant bacterial infections, and overexpression of multidrug efflux (MEX) transport systems has been identified as one of the most critical mechanisms facilitating the...


Acid suppression has been associated with adverse events; such as, enteric infections. Proton pump inhibitors (PPI) are frequently prescribed in patients with cirrhosis, but is unclear if PPI are associated with the development of bacterial infections in these patients.

Discovery of Novel Enhancers of Isoniazid Toxicity in.

The number of effective first-line antibiotics for the treatment ofinfection is strongly limited to a few drugs. Due to emerging resistance against those drugs, second- and third-line antibiotics have been established in therapy with certain problems and also increasing mycobacterial resistance. An alternative to such novel drugs or combined therapeutic regimes which may reduce resistance development is finding enhancers of mycobacterial drug effectiveness, especially enhancers that counteract causative res...

Negative Regulation Gene Circuits for Efflux Pump Control.

Synthetic biologists aim to design biological systems for a variety of industrial and medical applications, ranging from biofuel to drug production. Synthetic gene circuits regulating efflux pump protein expression can achieve this by driving desired substrates such as biofuels, pharmaceuticals, or other chemicals out of the cell in a precisely controlled manner. However, efflux pumps may introduce implicit negative feedback by pumping out intracellular inducer molecules that control gene circuits, which th...

Proton Pump Inhibitors and the Risk of Dementia: is There a Link?

Dementia is one of the most common neurodegenerative disorder among older populations around the world, and the incidence is increasing. Many epidemiologic studies have considered the association between proton-pump inhibitors and dementia, yet the relationship is still controversial.The objective of this study was to validate whether or not proton-pump inhibitors is indeed associated with dementia.Materials (Subjects) and Methods: We searched for articles on clinical studies of dementia and proton pump inh...

Efficacy of "HLE"-a multidrug efflux-pump inhibitor-as a disinfectant against surface bacteria.

We evaluated the efficacy of a new disinfectant product, HLE, to inhibit multiple species of planktonic and biofilm bacterial cultures. The HLE disinfectant comprised of EDTA, lactic acid and hydrogen peroxide, and our data indicated that the disinfectant had effective antimicrobial and anti-biofilm activity even at low concentrations (0.15% to 0.4% HLE, v/v). Furthermore, the HLE disinfectant destabilized biofilm structures eradicated them due to the synergistic effect of EDTA and both antimicrobials (lact...

Discovery of dual GyrB/ParE inhibitors active against Gram-negative bacteria.

Even though many GyrB and ParE inhibitors have been reported in the literature, few possess activity against Gram-negative bacteria. This is primarily due to limited permeability across Gram-negative bacterial membrane as well as bacterial efflux mechanisms. Permeability of compounds across Gram-negative bacterial membranes depends on many factors including physicochemical properties of the inhibitors. Herein, we show the optimization of pyridylureas leading to compounds with potent activity against Gram-ne...

Proton pump inhibitors are associated to minimal and overt hepatic encephalopathy and increase mortality in cirrhotics.

Minimal hepatic encephalopathy (MHE) is a subclinical cognitive impairment frequently observable in cirrhotics. Proton pump inhibitors (PPIs) can contribute to small-bowel bacterial overgrowth but no study investigated the link between PPIs and MHE.

Efflux pumps and antimicrobial resistance: Paradoxical components in systems genomics.

Efflux pumps play a major role in the increasing antimicrobial resistance rendering a large number of drugs of no use. Large numbers of pathogens are becoming multidrug resistant due to inadequate dosage and use of the existing antimicrobials. This leads to the need for identifying new efflux pump inhibitors. Design of novel targeted therapies using inherent complexity involved in the biological network modeling has gained increasing importance in recent times. The predictive approaches should be used to de...

DeepEfflux: a 2D Convolutional Neural Network Model for Identifying Families of Efflux Proteins in Transporters.

Efflux protein plays a key role in pumping xenobiotics out of the cells. The prediction of efflux family proteins involved in transport process of compounds is crucial for understanding family structures, functions and energy dependencies. Many methods have been proposed to classify efflux pump transporters without considerations of any pump-specific of efflux protein families. In other words, efflux proteins protect cells from extrusion of foreign chemicals. Moreover, almost all efflux protein families hav...

N,N'-disubstituted cinnamamide derivatives potentiate ciprofloxacin activity against overexpressing NorA efflux pump Staphylococcus aureus 1199B strains.

A multi-step procedure has been described which afforded satisfactory yields of N,N'-disubstituted cinnamamides derived from N-Boc-protected amino acids (Boc-Gly, Boc-Val, Boc-Phe). The key step of this synthesis was a regioselective RedAl reduction of an amide function in presence of a carbamate group. Next, these cinnamamides were evaluated in co-admnistration with ciprofloxacin as efflux pump inhibitors against two S. aureus strains, NorA overexpressing SA1199B and wild type SA1199. In parallel, their i...

Adverse effects of proton pump inhibitors: fact or fake news?

The present review summarizes the past year's literature, both clinical and basic science, regarding potential adverse effects of proton pump inhibitors.

Isovalerylshikonin, a new resistance-modifying agent from Arnebia euchroma, supresses antibiotic resistance of drug-resistant Staphylococcus aureus.

Antimicrobial resistance is the greatest threat to the treatment of bacterial infectious diseases. The development of resistance-modifying agents represents a promising strategy to mitigate the spread of bacterial antibiotic resistance. A natural product, isovalerylshikonin (IVS), was isolated from traditional Chinese medicine Arnebia euchroma in this study, which exhibited marginal antibacterial activity against drug-resistant Staphylococcus aureus RN4220, with an MIC of 16 mg/L. In addition, a synergistic...

Proton pump inhibitors use and risk of hepatocellular carcinoma.

One cohort study using the Taiwan's database conducted by Kao et al published in Hepatology reported that proton pump inhibitors use was not associated with the risk of developing hepatocellular carcinoma in patients with chronic hepatitis B infection or chronic hepatitis C infection. The findings were compatible with our cohort analysis using the Taiwan's database showing no association between proton pump inhibitors use and hepatocellular carcinoma. In contrast, a recent case-control study using the Taiw...

Lean body weight dosing avoids excessive systemic exposure to proton pump inhibitors for children with obesity.

Children with obesity are more likely to suffer gastroesophageal reflux disease, requiring acid-suppression therapy with proton pump inhibitors (PPIs) and no guidelines regarding dosing.

Use of proton pump inhibitors and risk of ischemic events in the general population.

A potential increased risk of cardiovascular events has been suggested for proton pump inhibitors (PPIs), the most commonly prescribed drugs for the management of upper gastrointestinal disorders. We aimed to estimate the risk of hospitalization for cardio/cerebrovascular (CV) events in a cohort of incident PPI users.

Maternal adherence to guidance on breast milk collection process.

Breast milk expression with a breast pump increases the risk of contaminating milk with pathogenic bacteria; how to decontaminate breast pumps is controversial. The aim of this study was to investigate maternal adherence to updated French guidance on the breast milk collection process, including breast pump decontamination, and to identify potential sources of increased bacterial counts in breast milk in order to improve prevention messages to mothers.

Treatment with platelet aggregation inhibitors and additive proton pump inhibitors?

Proton Pump Inhibitors (PPIs) are inhibitors or risk factor for Atrial Fibrillation?

Intramacrophage Mycobacterium tuberculosis efflux pump gene regulation after rifampicin and verapamil exposure.

Since resistance of Mycobacterium tuberculosis (Mtb) partially derives from efflux pumps (EPs) in the plasma membrane, the current study evaluates EPs in Mtb exposed to rifampicin in the presence of the EP inhibitor verapamil, within a macrophage environment.

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