Abstract: The invention provides systems and methods for increased clinical efficacy of rifabutin against A. baumannii. The invention takes advantage of the discovery of a ferric-coprogen (FhuE) receptor that is responsible for the uptake of rifabutin into A. baumannii cells. Methods preferably include obtaining a sample from a patient suspected of having an infection; performing a test on the sample to identify an infection of A. baumannii in the patient; and providing a formulation of rifabutin for treating the patient that, when administered to the patient, maximizes a resultant AUC and/or Cmax. The method may include administering the formulation of rifabutin to the patient. Preferably the formulation is delivered to the patient, e.g., by intravenous injection and results in a Cmax is that greater than about 2 mg/L and optionally less than about 50 mg/L.

Abstract: The invention provides antibiotic combination therapies for treating an A. baumannii infection in a subject. The combination therapies include rifabutin and a second antibiotic, such as colistin and cefiderocol.

Abstract: The invention provides systems and methods for increased clinical efficacy of rifabutin against A. baumannii. The invention takes advantage of the discovery of a ferric-coprogen (FhuE) receptor that is responsible for the uptake of rifabutin into A. baumannii cells. Methods preferably include obtaining a sample from a patient suspected of having an infection; performing a test on the sample to identify an infection of A. baumannii in the patient; and providing a formulation of rifabutin for treating the patient that, when administered to the patient, maximizes a resultant AUC and/or Cmax. The method may include administering the formulation of rifabutin to the patient. Preferably the formulation is delivered to the patient, e.g., by intravenous injection and results in a Cmax is that greater than about 2 mg/L and optionally less than about 50 mg/L.

Abstract: The invention provides antibiotic combination therapies for treating an A. baumannii infection in a subject. The combination therapies include rifabutin and a second antibiotic, such as colistin and cefiderocol.

Abstract: The invention provides systems and methods for increased clinical efficacy of rifabutin against A. baumannii. The invention takes advantage of the discovery of a ferric-coprogen (FhuE) receptor that is responsible for the uptake of rifabutin into A. baumannii cells. Methods preferably include obtaining a sample from a patient suspected of having an infection; performing a test on the sample to identify an infection of A. baumannii in the patient; and providing a formulation of rifabutin for treating the patient that, when administered to the patient, maximizes a resultant AUC and/or Cmax. The method may include administering the formulation of rifabutin to the patient. Preferably the formulation is delivered to the patient, e.g., by intravenous injection and results in a Cmax is that greater than about 2 mg/L and optionally less than about 50 mg/L.

Abstract: The invention provides antibiotic combination therapies for treating an A. baumannii infection in a subject. The combination therapies include rifabutin and a second antibiotic, such as colistin and cefiderocol.

Abstract: The invention provides systems and methods for increased clinical efficacy of rifabutin against A. baumannii. The invention takes advantage of the discovery of a ferric-coprogen (FhuE) receptor that is responsible for the uptake of rifabutin into A. baumannii cells. Methods preferably include obtaining a sample from a patient suspected of having an infection; performing a test on the sample to identify an infection of A. baumannii in the patient; and providing a formulation of rifabutin for treating the patient that, when administered to the patient, maximizes a resultant AUC and/or Cmax. The method may include administering the formulation of rifabutin to the patient. Preferably the formulation is delivered to the patient, e.g., by intravenous injection and results in a Cmax is that greater than about 2 mg/L and optionally less than about 50 mg/L.

Abstract: The present invention relates to a compound according to formula (I), wherein R1 and R5 are independently selected from H, halogen, hydroxyl, NO2, CN, C1-C6-alkyl optionally substituted by one or more R11, C1-C6-alkoxy optionally substituted by one or more R11, C3-C6-cycloalkyl optionally substituted by one or more R11, —Cn-alkyl-N(R12)(R13) with n=0-3, —Cn-alkyl-C(O)N(R12)(R13) with n=0-3, —SO2—N(R14)-C(O)—R15; —Cn-alkyl-N(R14)-C(O)—R15 with n=0-3, —Cn-alkyl-C(O)—OR16 with n=0-3, —O(C1-C3-alkyl-O)m—C1-C3-alkyl-OR10 with m=0-3, —Cn-alkyl-OR16 with n=0-3, —NH—Cn-alkyl-R18 with n=0-3; —O—Cn-alkyl-R18 with n=0-3; —OPO(OR10)2, —PO(OR10)2, and a heterocycle optionally substituted by one or more R17; R3 is selected from halogen, hydroxyl, NO2, CN, C1-C6-alkyl optionally substituted by one or more R11, C1-C6-alkoxy optionally substituted by one or more R11, C3-C6-cycloalkyl optionally substituted by one or more R11, —Cn-alkyl-N(R12)(R13) with n=0-3, —Cn-alkyl-C(O)N(R12)(R13) with n=0-3, —SO2—N(R14)-C(O)—R15; —Cn-alk

Abstract: The invention provides antibiotic combination therapies for treating an A. baumannii infection in a subject. The combination therapies include rifabutin and a second antibiotic, such as colistin and cefiderocol.

Abstract: The present invention relates to the field of bacterial vectors and methods for genetic manipulation of bacteria. In particular, the present invention relates to a vector for genetic manipulation of a bacterium, wherein said vector comprises (a) a non-antibiotic selection marker gene cassette, (b) an origin of replication, wherein said origin of replication is not capable of inducing replication of said vector in said bacterium, and (c) a restriction endonuclease gene, a recognition site of a restriction endonuclease encoded by said restriction endonuclease gene, and a second regulatory sequence. Further, the invention relates to a bacterial host cell comprising said vector, a method for genetic manipulation of bacteria using the vector of the invention, and methods for selecting bacterial host cells.

Abstract: The invention provides systems and methods for increased clinical efficacy of rifabutin against A. baumannii. The invention takes advantage of the discovery of a ferric-coprogen (FhuE) receptor that is responsible for the uptake of rifabutin into A. baumannii cells. Methods preferably include obtaining a sample from a patient suspected of having an infection; performing a test on the sample to identify an infection of A. baumannii in the patient; and providing a formulation of rifabutin for treating the patient that, when administered to the patient, maximizes a resultant AUC and/or Cmax. The method may include administering the formulation of rifabutin to the patient. Preferably the formulation is delivered to the patient, e.g., by intravenous injection and results in a Cmax is that greater than about 2 mg/L and optionally less than about 50 mg/L.

Abstract: The invention provides antibiotic combination therapies for treating an A. baumannii infection in a subject. The combination therapies include rifabutin and a second antibiotic, such as colistin and cefiderocol.

Abstract: The invention relates to vectors and mammalian cells in a system useful for switching on or switching off gene expression in response to uric acid. In a particular embodiment the invention relates to a mammalian cell useful in detecting and/or degrading a harmful excess of uric acid comprising (a) a vector comprising a genetic code for the uricase sensor-regulator HucR from Deinococcus radiodurans R1 fused to a transactivation domain or a transrepressor domain; and (b) a vector comprising the corresponding operator sequence hucO from Deinococcus radiodurans R1 specifically binding the bacterial uric acid sensor-regulator HucR, a promoter and a polynucleotide coding for an endogenous or exogenous protein, e.g. a protein interacting with uric acid.

Abstract: The invention relates to microcapsules consisting of a polymer degradable by a polypeptide comprising a drug or other compound of interest and a genetically engineered cell expressing said polypeptide in response to a triggering compound, and to methods of directed release of the compound of interest. The preferred polymer is optionally modified cellulose sulfate/poly-diallyl-dimethyl-ammonium chloride. Such microcapsules are non-toxic, do not elicit an immunological response and have an extended half-life time in mammals. The expression system for cellulase is, for example, based on TET and doxycycline, or E.REX and erythromycin. In another example, expression of cellulase is triggered by luteinizing hormone, which can be used for artificial insemination with microcapsules carrying sperm.

Abstract: The invention relates to microcapsules consisting of a polymer degradable by a polypeptide comprising a drug or other compound of interest and a genetically engineered cell expressing said polypeptide in response to a triggering compound, and to methods of directed release of the compound of interest. The preferred polymer is optionally modified cellulose sulfate/poly-diallyl-dimethyl-ammonium chloride. Such microcapsules are non-toxic, do not elicit an immunological response and have an extended half-life time in mammals. The expression system for cellulase is, for example, based on TET and doxycycline, or E.REX and erythromycin. In another example, expression of cellulase is triggered by luteinizing hormone, which can be used for artificial insemination with microcapsules carrying sperm.

Abstract: The invention relates to microcapsules consisting of a polymer degradable by a polypeptide comprising a drug or other compound of interest and a genetically engineered cell expressing said polypeptide in response to a triggering compound, and to methods of directed release of the compound of interest. The preferred polymer is optionally modified cellulose sulfate/poly-diallyl-dimethyl-ammonium chloride. Such microcapsules are non-toxic, do not elicit an immunological response and have an extended half-life time in mammals. The expression system for cellulase is, for example, based on TET and doxycycline, or E.REX and erythromycin. In another example, expression of cellulase is triggered by luteinizing hormone, which can be used for artificial insemination with microcapsules carrying sperm.

Abstract: The invention relates to vectors and mammalian cells in a system useful for switching on or switching off gene expression in response to uric acid. In a particular embodiment the invention relates to a mammalian cell useful in detecting and/or degrading a harmful excess of uric acid comprising (a) a vector comprising a genetic code for the uricase sensor-regulator HucR from Deinococcus radiodurans R1 fused to a transactivation domain or a transrepressor domain; and (b) a vector comprising the corresponding operator sequence hucO from Deinococcus radiodurans R1 specifically binding the bacterial uric acid sensor-regulator HucR, a promoter and a polynucleotide coding for an endogenous or exogenous protein, e.g. a protein interacting with uric acid.

Abstract: The invention relates to microcapsules consisting of a polymer degradable by a polypeptide comprising a drug or other compound of interest and a genetically engineered cell expressing said polypeptide in response to a triggering compound, and to methods of directed release of the compound of interest. The preferred polymer is optionally modified cellulose sulfate/poly-diallyl-dimethyl-ammonium chloride. Such microcapsules are non-toxic, do not elicit an immunological response and have an extended half-life time in mammals. The expression system for cellulase is, for example, based on TET and doxycycline, or E.REX and erythromycin. In another example, expression of cellulase is triggered by luteinizing hormone, which can be used for artificial insemination with microcapsules carrying sperm.