124 results about "Efflux" patented technology

This invention relates to the field of antimicrobial agents and more specifically it relates to Efflux Pump Inhibitor (EPI) compounds to be co-administered with antimicrobial agents for the treatment of infections caused by drug resistant pathogens. The EPI compounds are soft drugs which exhibit a reduced propensity for tissue accumulation. The invention includes novel compounds useful as efflux pump inhibitors, compositions and devices comprising such efflux pump inhibitors, and therapeutic use of such compounds.

Efflux pump inhibitors are co-administered with antimicrobial agents for the treatment of ophthalmic or otic infections. The agents may be co-administered directly to the site of infection (e.g., the eye or ear).

A medicament for preventive and / or therapeutic treatment of a microbial infection which comprises as an active ingredient a compound represented by the following general formula (I): wherein, R1 and R2 represent hydrogen atom, a halogen atom, hydroxyl group or the like, W1 represents —CH═CH—, —CH2O—, —CH2CH2— or the like; R3 represents hydrogen atom, a halogen atom, hydroxyl group or an amino group; R4 represents hydrogen atom, a group of —OZ0-4R5 (Z0-4 represents an alkylene group, a fluorine-substituted alkylene group or a single bond, and R5 represents a cyclic alkyl group, an aryl group or the like); W2 represents a single bond or —C(R8)═C(R9)— (R8 and R9 represent hydrogen atom, a halogen atom, a lower alkyl group or the like, Q represents an acidic group, but W2 and Q may together form vinylidenethiazolidinedione or an equivalent heterocyclic ring; m and n represent an integer of 0 to 2, and q represents an integer of 0 to 3.

The present invention describes the use of polysaccharides, surfactants, and dendrimers as bioavailability enhancers for oral pharmaceutical compositions. These substances exhert an inhibitory action of the gastrointestinal pump efflux proteins, such as the P-glycoprotein and the MDR protein, responsible for poor drug bioavailability and multidrug resistance. The formulations herein described comprise a medicinally active substance in association with said polysaccharides, surfactants, and dendrimers. They are well tolerated, are not absorbed by the gastrointestinal tract, and increase the bioavailability and the activity of orally administered medicaments, like, e.g. antineoplastic, antiviral, antibiotic, or antidepressant medicaments.

The invention discloses an improved resveratrol biological production method, and relates to an improved construction method of a recombinant bacterium for producing resveratrol. The construction method comprises the following steps: (1) carrying out complete synthesis to obtain genes: synTAL, syn4CL, and synSTS; (2) preparing a SyBE-002447(DE3) strain; (3) carrying out complete synthesis to obtain a gene: synaccBC-dtsR1; (4) cloning an efflux protein gene yddG; (5) carrying out total chemical synthesis to obtain SyBE-217101 and pSyBE-217102; (6) connecting synTAL, syn4CL, and synSTS with pSyBE-217101 to obtain a recombinant expression vector pSyBE-synTLS; and connecting synaccBC-dtsR1 and yddG with pSyBE-217102 to obtain a recombinant expression vector pSyBE-synADY; and (7) converting tworecombinant expression vectors into the SyBE-002447(DE3) strain, and carrying out monoclonal screening to obtain a recombinant bacterium SyBEREST. Through expressing the efflux protein, the secretionof resveratrol is promoted, the yield of resveratrol is obviously increased, and the cost is reduced.

Macrolide resistance associated with macrolide efflux (mef) in Streptococcus pneumoniae has been defined with respect to the genetic structure and dissemination of a novel mefE-containing chromosomal insertion element. The mefE gene is found on the 5′-end of a 5.5 kb or 5.4 kb insertion designated mega (macrolide efflux genetic assembly) found in at least four distinct sites of the pneumococcal genome. The element is transformable and confers macrolide resistance to susceptible S. pneumoniae. The first two open reading frames (ORFs) of the element form an operon composed of mefE and a predicted ATP-binding cassette homologous to msrA. Convergent to this efflux operon are three ORFs with homology to stress response genes of Tn5252. Mega is related to mefA-containing element Tn1207.1. Macrolide resistance due to mega has been rapidly increased by clonal expansion of bacteria containing it and horizontally by transformation of previously sensitive bacteria.

The invention relates to an antibacillus pyocyaneus drug screening model which selects bacillus pyocyaneus external discharge pump adventitial protein MexAB-OprM as bull's-dot and to a method of screening antibacillus pyocyaneus drug using the said screening model. The invention also relates to a recombination bacillus pyocyaneus of excess expression MexAB-OprM protein which can be used in the said screening model and the screening method. The invention also relates to the antibacillus pyocyaneus drug obtained by the said screening model and method.

Disclosed are compounds having at least one quaternary alkyl ammonium functionality. The compounds inhibit bacterial efflux pump inhibitors and are used in combination with an anti-bacterial agent to treat or prevent bacterial infections. These combinations can be effective against bacterial infections that have developed resistance to anti-bacterial agents through an efflux pump mechanism.

Disclosed herein are polybasic bacterial efflux pump inhibitors containing boronic acid functionality and their methods of synthesis, methods of use, and pharmaceutical compositions. Some embodiments include methods of treating or preventing a bacterial infection by co-administering to a subject infected with bacteria or at risk of infection with bacteria the efflux pump inhibitor with another anti-bacterial agent.

The invention provides an integrated zero-leakage gas positive-negative pressure compatible microorganism isolation operation cabinet which comprises a positive pressure cabin with a positive pressure fan and a sterile filter at the top and a glass sliding door, wherein the positive pressure cabin is surrounded by a glass front partition plate and a glass side partition plate to form a negative pressure cabin; two sealed isolation sleeves formed by overlapping and interacting an outer partition soft plate and an inner partition soft plate are arranged on the glass front partition plate; on a working table of the negative pressure cabin, a circle of negative-pressure air grid ports are communicated with a negative pressure filtering cabin with a gas filtering material; and the negative pressure fan is arranged in a fan chamber communicated on the lower side of the negative pressure filtering cabin to extract the filtered waste gas to an exhaust connector to be discharged. The zero-leakage gas positive-negative pressure compatible microorganism isolation operation cabinet provided by the invention has the beneficial effects that the device can ensure that the cells and bacteria cultured in a microorganism experiment process are free from the contamination and interference of other bacteria in a sterile positive pressure environment, and harmful microorganisms and gases inside can be isolated and shielded by the negative pressure cabin so as to prevent leakage and consequent environmental pollution and occupational injury; and the device is widely applied to the scientific research fields such as environmental protection, medical scientific research, military security and the like.

The invention relates to a selenium nano composite material capable of overcoming multi-drug-resistant bacterial infection. The selenium nano composite material comprises nano-selenium composite particles, which are obtained by coating mannose modified chitosan on the outer surface of a complex of selenium nano particles and beta-lactam antibiotics, and are of a spherical structure, wherein selenium nanoparticles and beta-lactam antibiotics are arranged in the nano-selenium composite particles, mannose-modified chitosan is arranged on the outer surface of the nano-selenium composite particles,the average particle size of the nano-selenium composite particles is 40-80 nm, and the thickness of shells of the mannose-modified chitosan on the surface is smaller than or equal to 5 nm. The invention also provides a selenium nano composite material capable of overcoming multi-drug-resistant bacterial infection, and application of the selenium nano composite material in a nano antibacterial material. The nano antibacterial material prepared by the invention inhibits the expression of a drug efflux pump of multi-drug-resistant bacteria and the activity of beta-lactamase, and chitosan is used for embedding selenium nanoparticles and antibiotics, so that the dispersity and stability of the nano material are favorably improved.

Disclosed are compounds having polybasic functionalities. The compounds inhibit bacterial efflux pump inhibitors and are used in combination with an anti-bacterial agent to treat or prevent bacterial infections. These combinations can be effective against bacterial infections that have developed resistance to anti-bacterial agents through an efflux pump mechanism.

The invention relates to a preparation method and applications of an oral absorption enhancer built based on a natural P-glycoprotein (P-gp) inhibitor. The preparation method is implemented through grafting natural small molecules with a P-gp efflux inhibition function to a chitosan derivative through chemical coupling, so that the oral absorption enhancer with a P-gp efflux inhibition function is synthesized. The oral absorption enhancer has the following characteristics: (1) after the small molecules with the P-gp efflux inhibition function are coupled with the chitosan derivative, a synthesized conjugate has the P-gp efflux inhibition function, and can promote the absorption of drugs in gastrointestinal tracts by inhibiting the efflux of P-gp; (2) the synthesized conjugate can be independently used as a new polymer drug; and (3) the synthesized conjugate has amphipathy, and can be self-assembled in water so as to form a micelle for encapsulating a hydrophobic antitumor drug, so that the water solubility of drugs is increased, the drug intake of gastrointestinal tracts is increased, and the bioavailability of drugs is improved. The preparation method disclosed by the invention is simple, low in cost, and suitable for large-scale continuous production.

The invention discloses a new process for purifying cytochrome C, which comprises the following steps: (1) extracting cytochrome C coarse extract from animal organs or yeasts; (2) adding an inorganic salt into the coarse extract to perform salting, standing, centrifuging and removing settled proteins, and collecting supernate; (3) adding buffer solution to regulate the inorganic salt concentration in the supernate to 20 to 35 percent, and purifying the supernate by using front-end hydrophobic chromatography, namely continuously loading the obtained solution onto a hydrophobic chromatographic column which is balanced by inorganic salt solution at a concentration of 20 to 35 percent in advance and collecting penetration solution; and (4) washing the chromatographic column by using the inorganic salt solution at a concentration of 20 to 35 percent till a stable light absorbance, collecting the efflux of the chromatographic column, mixing the efflux of the chromatographic column with penetration solution, and purifying to obtain cytochrome C. In the invention, the operation is simple and convenient, the separation and purification effect is good, the yield is high and cost is low.

The invention relates to a preparation method of a nano delivery system between targeted redox-sensitive co-load chemotherapeutic drugs and P-gp resistance reversal agents. The redox-sensitive amphiphilic copolymers PCL7500-ss-PEG7500-ss-PCL7500 is utilized to build redox-sensitive polymer vesicle, intermolecular hydrophobic force is used to load hydrophobic taxol and Tarigquidar, adriamycin is loaded inside the hydrophilic chamber of the polymer vesicle via pH gradient method, folate targeting group is decorated on the surface of the polymer vesicle via covalent bond, thereby the polymer vesicle with synergistic activity with targeting, reduction and response and chemotherapy is built. P-glycoprotein(P-gp) of small molecules inhibitor Tariguidar reduces the drug resistance of drug resistance cells by blocking the efflux function of P-gp to the base drug, the picking up of drugs of drug resistance cells is increased, thereby the multiple drug resistance is reversed. The nano delivery system is capable of loading hydrophobic drugs and hydrophilic drugs, tumor targeting and having reducing and response to the tumor micro environment and realizing killing tumors by reserving the multiple drug resistance.

The invention discloses an application of liquiritin in preparing an escherichia coli fluoroquinolone efflux pump inhibitor. Research results indicate that, the liquiritin can obviously reduce the minimal inhibitory concentration of fluoroquinolone of drug-resistant escherichia coli (fluoroquinolone active efflux phenotype and acrA gene high expression strain), obviously increase drug accumulation concentration in a thallus, and obviously reduce expression quantity of an efflux pump gene acrA, so that susceptibility of the drug-resistant escherichia coli to the fluoroquinolone is increased, usage amounts of drugs are reduced, treatment cost is reduced, and food safety problems such as drug residues are decreased. Simultaneously, the liquiritin is a natural compound existing in plants, has no side effects such as teratogenesis and carcinogenesis, and is safe and nontoxic. The invention not only broadens application fields of the liquiritin and improves market value of the liquiritin, but also provides an efficient and safe bacteria efflux pump inhibitor for anti-infective therapy.

The invention belongs to the technical field of biological engineering and discloses a method for improving rice potassium ion efflux antiporter. A function mutant strain of rice potassium ion efflux antiporter protein is obtained by a KEA1 gene for mutation control of rice potassium ion efflux and protein encoded by the gene; meanwhile, gamma rays are utilized to treat 9522 strain of japonica rice, and mutants of which the leaf veins are whitened are selected in F2 generation after the rice is planted so as to obtain the function mutant strain of the rice potassium ion efflux antiporter protein. By utilizing the characteristic that the protein participates in chloroplast potassium ion efflux antiporter and controls rice potassium ion transport by a transgenic technology, a new rice stress-resistant line is generated by inhibiting the expression of the protein, and has important application value in agricultural production.

The present invention relates to a method for the fermentative preparation of O-acetyl-L-serine, in which a microbial strain is cultured in a fermentation medium, the microbial strain being derived from a wild type and showing increased O compared to the wild type Endogenous formation of -acetyl-L-serine and increased efflux of O-acetyl-L-serine, the method includes setting the pH in the fermentation medium in the range of 5.1 to 6.5.

The invention belongs to the field of a biological medicine, and relates to application of euphoriafactor L1 (euphoriafactor L1, EFL1) used as a multidrug resistance reversal agent for tumors, especially relates to treatment of multidrug resistance tumors by combining with antitumor drugs, so as to restore the sensitivity of tumor cells to the anti-cancer drugs. The invention also relates to a mechanism of the euphoriafactor L1 for reversing the multidrug resistance of the tumors, namely multidrug resistance (MDR) of ABCB1-mediaed tumor cells are reversed by enhancing ATP enzymatic activity of ABCB1 in the tumor cells and inhibiting an efflux function of the ABCB1; ABCB1 expression in MDR cells in messenger ribonucleic acid (mRNA) or protein level is not reduced.

The present invention provides methods and compositions for increasing the susceptibility of PDF inhibitors against Gram-negative organisms by using efflux pump inhibitors.

The invention relates to the field of antimicrobial agents, and to methods for the identification and characterization of potential antimicrobial agents and compounds which enhance the effect of antimicrobial agents. More specifically this invention relates to methods for screening agents for which the mode of action involves the acrAB family of efflux pumps.

The invention belongs to the technical field of research on the drug resistance of microorganisms, and provides a siRNA-DNA nanometer system for targetedly inhibiting Salmonella drug-resistance effluxpump gene acrA, and a preparation method thereof, specifically a DNA nanometer vector, which has a tetrahedron-like structure formed by assembling an oligonucleotide A single chain, an oligonucleotide B single chain, and an oligonucleotide C single chain. Based on the DNA nanometer vector, the present invention further provides a nanometer system, a preparation method and applications thereof, wherein the DNA nanometer vector loads a siRNA targeting efflux pump gene to from the nanometer system. According to the present invention, the DNA nanometer vector has the tetrahedron-like structure, can stably load siRNA, and can safely, rapidly and efficiently transport the siRNA to target cells so as to inhibit the expression of the Salmonella efflux pump gene, such that the sensitivity on antibiotics by Salmonella is improved so as to effectively inhibit the drug resistance of Salmonella.

The invention discloses a method for obtaining outer membrane vesicles (OMVs) of escherichia coli and klebsiella pneumoniae by utilizing an ultrafiltration and concentration method. The method comprises the following steps of making the escherichia coli and the klebsiella pneumoniae into bacterial suspension, taking and inoculating a proper amount of the bacterial suspension into a test tube containing a culture medium for culturing and staying overnight, then taking and inoculating a proper amount of a bacterial solution into a shake flask containing a culture medium l for culturing until an OD (Optical Density) value approaches 1.0, collecting the bacterial solution, centrifuging the bacterial solution to remove a thallus, filtering the bacterial solution by a sterile filter head to remove a residual thallus, collecting filtrate, centrifugally concentrating the filtrate until 1 / 8 of an original volume by an ultrafiltration tube with a molecular weight cutoff of 100KDa, adding normal saline into the filtrate for washing, repeating the step for 2 to 3 times, collecting the bacterial outer membrane vesicles located on an upper layer of the ultrafiltration tube, and putting the bacterial outer membrane vesicles in an environment at subzero 20 DEG C for subpackaging and cryopreserving, wherein the protein concentration of the extracted outer membrane vesicle of the klebsiella pneumoniae is 1.5mg / ml; the protein concentration of the extracted outer membrane vesicle of the escherichia coli is 2.1mg / ml; the particle sizes of the OMVs are approximately 20nm to 100nm. The method is convenient, simple, easy and feasible to operate; a novel method is provided for the extraction and the research of the OMVs.

The invention discloses an engineering probiotic capable of displaying phenylalanine ammonialyase on the surface, which is an escherichia coli Nissle 1917 derived bacterium, a gene argR is knocked out and / or a gene argA (Y19C) mutation is generated on a genome, and an L-phenylalanine ammonialyase gene stlA, an L-phenylalanine transport protein gene pheP, an L-amino acid deaminase gene pma and an efflux pump gene acrA are integrated. The engineering probiotics can be used for treating phenylketonuria.

An antimicrobial composition for the treatment of drug-resistant pathogens is provided. The composition includes antimicrobial compounds and chelating agents assemblies that are particularly effective in inhibiting drug-resistant bacteria and biofilm growth. Optionally, the composition may include an efflux pump inhibitor, further enhancing activity against resistant bacteria. Also provided are methods of treating diseases and surfaces of materials treated with the composition.

The invention discloses a recombinant escherichia coli strain for producing 5-aminolevulinic acid (5-ALA). The invention also discloses a way for efficiently synthesizing the 5-aminolevulinic acid, wherein the 5-aminolevulinic acid synthetase (HemL and HemA) of the escherichia coli is enhanced, and the strain has the capability of synthesizing the 5-aminolevulinic acid preliminarily; the expression of the 5-aminolevulinic acid efflux protein eamA gene is enhanced, and the 5-aminolevulinic acid efflux capability of the strain is improved; an exogenous 5-aminolevulinic acid synthetase hemA gene is introduced, so that the 5-aminolevulinic acid synthesis capability of the strain is enhanced; galR, glk and ppc genes of a glucose utilization way are modified, and the utilization efficiency of glucose is improved; and genes (hemF, poxB and aceB) of metabolic bypasses are knocked out. The recombinant Escherichia coli strain constructed by the invention has the capability of efficiently synthesizing 5-aminolevulinic acid by using glucose and glycine, so that the recombinant Escherichia coli strain has the application of industrially producing 5-aminolevulinic acid.

The invention belongs to the pharmaceutical field, relates to beta,beta-dimethyl-acry-lalkannin and an application in preparing medicines for inhibiting drug-resistant bacteria. The invention can provide a natural inhibitor for inhibiting efflux pump multidrug methicillin-resistant staphylococcus aureus. The compound has good inhibiting effect on multidrug staphylococcus aureus resistance strain with NorA efflux pump protein and the antibacterial effect is 13 times of positive contrastive drug norfloxacin. The compound can both inhibit tetracycline-resistant staphylococcus aureus strain Xu212with TetK tetracycline efflux pump protein and macrolide-resistant staphylococcus aureus strain RN4220 with MsrA macrolide efflux pump protein, and the minimal inhibitory concentration is 10.8mu m. The compound of the invention can be prepared to medicines for inhibiting multidrug resistance bacteria and produced to antibacterial injection or external medicine preparation.