A5020678543- Antibiotic Resistance in Bacteria
- Drug Transport and Resistance Mechanisms
- Antibiotics Pharmacokinetics and Efficacy
- Bacterial Genetics and Biotechnology
- Pneumonia and Respiratory Infections
- Lipid Membrane Structure and Behavior
- Biochemical Analysis and Sensing Techniques
- Tuberculosis Research and Epidemiology
- Pharmaceutical and Antibiotic Environmental Impacts
- Gut microbiota and health
- Bacterial biofilms and quorum sensing
- Antioxidant Activity and Oxidative Stress
- Cancer therapeutics and mechanisms
- Radiopharmaceutical Chemistry and Applications
- Neuroscience and Neuropharmacology Research
- Gastroesophageal reflux and treatments
- Microbial Community Ecology and Physiology
- Probiotics and Fermented Foods
- Bacterial Infections and Vaccines
Osaka University
2017-2023
Osaka Research Institute of Industrial Science and Technology
2017-2021
Osaka University of Pharmaceutical Sciences
2017
University of Groningen
2013-2014
A wide variety of phytochemicals are consumed for their perceived health benefits. Many these have been found to alter numerous cell functions, but the mechanisms underlying biological activity tend be poorly understood. Phenolic particularly promiscuous modifiers membrane protein function, suggesting that some actions may due a common, bilayer-mediated mechanism. To test whether bilayer perturbation underlie this diversity actions, we examined five bioactive phenols reported medicinal...
AcrB is the major multidrug exporter in Escherichia coli. Although several substrate-entrances have been identified, specificity of these various transport paths remains unclear. Here we present evidence for a substrate channel (channel 3) from central cavity trimer, which connected directly to deep pocket without first passing switch-loop and proximal . Planar aromatic cations, such as ethidium, prefer 3 channels 1 2. The efflux through increases by targeted mutations not competition with...
Drug efflux pumps transport antimicrobial agents out of bacteria, thereby reducing the intracellular concentration, which is associated with intrinsic and acquired bacterial resistance to these antimicrobials. As genome analysis has advanced, many drug pump genes have been detected in genomes species. In addition resistance, are involved various essential physiological functions, such as adaptation hostile environments, toxin metabolite efflux, biofilm formation quorum sensing. Gram-negative...
Abstract Multidrug resistance in Gram-negative bacteria can arise by the over-expression of multidrug efflux pumps, which extrude a wide range antibiotics. Here we describe ancestral Haemophilus influenzae pump AcrB (AcrB-Hi). We performed phylogenetic analysis hundreds RND-type transporters. found that AcrB-Hi is relatively ancient pump, nonetheless export same antibiotics as its evolved colleague from Escherichia coli . was not inhibited inhibitor ABI-PP, and could bile salts weakly. This...
The overexpression of RND-type exporters is one the main causes multidrug resistance (MDR) in Gram-negative pathogens. In RND transporters, such as Escherichia coli's efflux pump AcrB, drug occurs porter domain, while protons flow through transmembrane domain: remote conformational coupling. At border a helix (TM8) and subdomain PC2, there loop which makes hoisting movement by random-coil-to-α-helix change, opens closes channel entrance. This supposed to play key role allosteric coupling...
Recent mutations in RND efflux pumps clinical strains have further increased multidrug resistance. We show that R717L and R717Q substitutions (found azithromycin-resistant Salmonella enterica spp.) the Escherichia coli pump AcrB dramatically increase macrolide, as well fluoroquinolone, On other hand, cells became more susceptible to novobiocin β-lactam cloxacillin. urge control of, adjustments to, treatments with antibiotics need for novel inhibitors.
The multidrug efflux transporters MexB and MexY in Pseudomonas aeruginosa AcrB Escherichia coli contribute to these organisms' resistance. Efflux pump inhibitor (EPI) ABI-PP inhibits AcrB, but not MexY. We previously determined the structure of bound hydrophobic trap (the inhibitor-binding pit) MexB. insensitivity was attributed a bulky tryptophan (Trp). AcrB(Phe178Trp) became uninhibited by ABI-PP, while MexY(Trp177Phe) resensitized for ABI-PP. Interestingly, able inhibit MexB(Phe178Trp)....
Indole is a signal molecule derived from the conversion of tryptophan, and it present in bacterial respiratory gas. Besides influencing growth, indole exhibits effects on human health, including positive effect inflammation protection against pathogens. However, high fecal concentration (FIC) can suggest an unbalanced gut flora or presence certain To analyze produced by bacteria, its collection detection required. Traditional methods usually require centrifugation liquid culture medium...
Abstract Multidrug resistance (MDR) in bacteria can be caused by the over-expression of multidrug efflux pumps belonging to Resistance-Nodulation-Division (RND) superfamily proteins. These intrinsic or acquired export a wide range antibiotics. Recently, amino acid substitutions within these have been observed resistant clinical strains. Among others, two worrying gain-of-function mutations are R717L and R717Q proximal binding pocket pump AcrB (AcrB-Sa) found azithromycin-resistant Salmonella...