112 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.

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 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 production of O-acetyl-L-serine, in which method a microbial strain is cultured in a fermentation medium, the microbial strain is derived from the wild type and exhibits an increased O -Endogenous formation of acetyl-L-serine and increased efflux of O-acetyl-L-serine, the method comprising 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 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.

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.

The invention discloses a recombinant bacterium capable of producing L-homoserine at high yield as well as a preparation method and application of the recombinant bacterium. The recombinant bacterium provided by the invention is obtained by transforming the following two ways A) and B) in a chassis host bacterium: A) a metabolic way from fumaric acid to aspartic acid in the chassis host bacterium is enhanced, so that the metabolic flow of the two ways from oxaloacetic acid to L-aspartic acid and the metabolic flow of the two ways from fumaric acid to L-aspartic acid are matched in a ratio of 1: 1; and B) a metabolic pathway from aspartic acid to homoserine in the chassis host bacteria is enhanced; The method has the following advantages: 1, the iclR gene is knocked out; 2, an L-homoserine efflux pump gene rthB is used; and 3, two synthesis routes of L-aspartic acid, namely an oxaloacetic acid OAA synthesis route and a fumaric acid FUM synthesis route, are accurately regulated and controlled, so that the two synthesis fluxes are matched in a ratio of 1: 1, the reduction force balance in the fermentation process of the L-homoserine is realized, and the yield of the L-homoserine is maximized.

Novel compounds are disclosed having the structure of Formula I:

The compounds are potent bacterial efflux pump inhibitors (EPIs). Such compounds are useful to potentiate the antimicrobial activity of antimicrobial compounds such as beta-lactam antibiotics and quinolone antibiotics against Gram-negative bacteria.

Disclosed herein are compounds of formula (I), or a salt thereof and compositions comprising compounds of formula I that exhibit antibacterial activities, when tested alone and/or in combination with a bacterial efflux pump inhibitor. Also disclosed are methods of treating or preventing a bacterial infection in an animal comprising administering to the animal a compound of formula I alone or in combination with the administration of a bacterial efflux pump inhibitor.

An empirical Screen for Anti-infectives using Fluorescence microscopy of IntracellulaR Enterobacteriaceae (SAFIRE) was developed. Using this methodology, a library of small molecules and identified antimicrobials that are cell permeable and non-host-toxic were screened. Inhibitors of bacterial efflux pumps were identified as being implicated in antibiotic resistance and are attractive therapeutic targets for antimicrobials.