Abstract: An important advance in the battle against drug resistance by elucidating the domains of MarA which are critical in mediating its function. Accordingly, MarA family protein helix-tun-helix domains, mutant MarA family protein helix-turn-helix domains and methods of their use, for example, in screening assays to identify compounds which are useful as antiinfective agents and in screening assays to identify loci which are involved in mediating antibiotic resistance are described.

Abstract: Substituted tetracycline compounds, methods of synthesis, and methods of use are discussed. Tetracyclines useful for treating tetracycline related disorders are also discussed. Intermediates useful for synthesizing other tetracycline compounds are also included.

Abstract: A method for modulating RNA with tetracycline compounds is described.

Abstract: Substituted tetracycline compounds, methods of synthesis, and methods of use are discussed. Tetracyclines useful for treating tetracycline related disorders are also discussed. Intermediates useful for synthesizing other tetracycline compounds are also included.

Abstract: The present invention provides an improved methodology by which therapeutically to overcome resistance to tetracycline in living cells including bacteria, parasites, fungi, and rickettsiae. The methodology employs a blocking agent such as C5 ester derivatives, or 6-deoxy 13-(substituted mercapto) derivatives of tetracycline, in combination with other tetracycline-type antibiotics as a synergistic combination of compositions to be administered simultaneously, sequentially or concurrently. In another embodiment, certain novel compositions are provided which may be administered alone against, for example, a sensitive or resistant strain of gram positive bacteria such as S. aureus and E. faecalis. The concomitantly administered compositions effectively overcome the tetracycline resistant mechanisms present such that the cell is effectively converted from a tetracycline-resistant state to a tetracycline-sensitive state.

Abstract: The invention includes new substituted tetracycline-type compounds that exhibit significant antibacterial activity, including against both gram-positive and gram-negative bacteria. It has been found that compounds of the invention are highly active against both gram positive and gram negative tetracycline sensitive and tetracycline resistant bacteria.

Abstract: The present invention provides an improved methodology by which therapeutically to overcome resistance to tetracycline in living cells including bacteria, parasites, fungi, and rickettsiae. The methodology employs a blocking agent such as C5 ester derivatives, or 6-deoxy 13-(substituted mercapto) derivatives of tetracycline, in combination with other tetracycline-type antibiotics as a synergistic combination of compositions to be administered simultaneously, sequentially or concurrently. In another embodiment, certain novel compositions are provided which may be administered alone against, for example, a sensitive or resistant strain of gram positive bacteria such as S. aureus and E. faecalis. The concomitantly administered compositions effectively overcome the tetracycline resistant mechanisms present such that the cell is effectively converted from a tetracycline-resistant state to a tetracycline-sensitive state.

Abstract: The current invention is based, inter alia, on the finding that the transcription factor MarA, and homologues of MarA, e.g., Rob and SoxS, are virulence factors. Accordingly, the invention discloses methods for screening compounds for their ability to modulate these virulence factors. The invention further describes methods for treating and preventing bacterial infections by modulating the expression and/or activity of transcription factors. In addition, the invention provides a method for identifying other virulence factors.

Abstract: Methods and compounds for treating diseases with tetracycline compounds having a target therapeutic activity are described.

Abstract: Methods and mutants for identifying an antimicrobial compound which interacts with an ER polypeptide are disclosed. In particular, the method pertains to screens for identifying an antimicrobial compound using FabI or InhA mutant cells or polypeptides.

Abstract: The instant methods and compositions represent an advance in controlling drug resistance in microbes. AcrAB-like efflux pumps have been found to control resistance to drugs, even in highly resistant microbes. Accordingly, methods of treating infection, methods of screening for inhibitors of AcrAB-like efflux pumps, and methods of enhancing antimicrobial activity of drugs are provided. Pharmaceutical composition comprising an inhibitor of an AcrAB-like efflux pump and an antimicrobial agent are also provided.

Abstract: Methods for identifying compound useful as anti-infectives that decrease resistance, virulence, or growth of microbes are provided. In one embodiment, the method comprises contacting a microbial cell comprising: 1) a selectable marker under the control of a transcription factor responsive element and 2) a transcription factor, with a compound under conditions which allow interaction of the compound with the microbial cell; and measuring the ability of the compound to affect the growth or survival of the microbial cell as an indication of whether the test compound modulates the activity of a transcription factor.

Abstract: Methods for identifying MarR family inhibiting compounds are described. The methods include the use of computer aided rational based drug design programs and three dimensional structures of MarR family polypeptides.

Abstract: The invention relates to methods and compositions for manipulating bacterial resistance to non-antibiotic antibacterial compositions, disinfectants and organic solvents. The invention provides methods for rendering bacterial cells susceptible to non-antibiotic antibacterial compositions. Also provided are methods to reduce the selection of bacterial mutants having an multiple antibiotic resistance phenotype by non-antibiotic antibacterial compositions. The invention also provides methods for testing the ability of non-antibiotic antibacterial compositions to select for or induce a multiple antibiotic resistance phenotype in bacteria. Also provided are methods for increasing or decreasing bacterial tolerance to organic solvents by increasing or decreasing the activity of bacterial organic solvent efflux pumps. Compositions useful in the foregoing methods are also provided.

Abstract: The present invention provides an improved methodology by which therapeutically to overcome resistance to tetracycline in living cells including bacteria, parasites, fungi, and rickettsiae. The methodology employs a blocking agent such as C5 ester derivatives, or 6-deoxy 13-(substituted mercapto) derivatives of tetracycline, in combination with other tetracycline-type antibiotics as a synergistic combination of compositions to be administered simultaneously, sequentially or concurrently. In another embodiment, certain novel compositions are provided which may be administered alone against, for example, a sensitive or resistant strain of gram positive bacteria such as S. aureus and E. faecalis. The concomitantly administered compositions effectively overcome the tetracycline resistant mechanisms present such that the cell is effectively converted from a tetracycline-resistant state to a tetracycline-sensitive state.

Abstract: The crystal structure of the MarR protein, a regulator of multiple antibiotic resistance in Escherichia coli, is described.

Abstract: Disclosed are synthetic oligonucleotides complementary to a transcript of the marORAB operon which inhibit expression of a gene in the operon. Also disclosed are methods of reducing bacterial resistance to antibiotics, and pharmaceutical formulations containing marORAB-specific oligonucleotides of the invention.

Abstract: An isolated and cloned region of a bacterial chromosome containing a multiple antibiotic resistance operon is disclosed. A description of the structure and function of the operon is provided as are-assorted recombinant DNA constructs involving the operon or fragments thereof. The diagnostic, therapeutic and experimental uses of these constructs are also disclosed. Methods of evaluating the antibiotic effectiveness of compositions are disclosed and methods of treatment employing effective compositions are provided.

Abstract: Disclosed are synthetic oligonucleotides complementary to a transcript of the marORAB operon which inhibit expression of a gene in the operon. Also disclosed are methods of reducing bacterial resistance to antibiotics, and pharmaceutical formulations containing marORAB-specific oligonucleotides of the invention.

Abstract: The instant methods and compositions represent an advance in controlling drug resistance in microbes. AcrAB-like efflux pumps have been found to control resistance to drugs, even in highly resistant microbes. Accordingly, methods of treating infection, methods of screening for inhibitors of AcrAB-like efflux pumps, and methods of enhancing antimicrobial activity of drugs are provided. Pharmaceutical composition comprising an inhibitor of an AcrAB-like efflux pump and an antimicrobial agent are also provided.