Abstract: The invention provides methods for administering a therapeutically effective amount of daptomycin while minimizing skeletal muscle toxicity. The methods provide daptomycin administration at a dosing interval of 24 hours or greater. This long dosing interval minimizes skeletal muscle toxicity and allows for higher peak concentrations of daptomycin, which is related to daptomycin's efficacy. The invention also provides methods of administering lipopeptide antibiotics other than daptomycin while minimizing skeletal muscle toxicity by administering a therapeutically effective amount of the lipopeptide antibiotic at a dosage interval that does not result in muscle toxicity. The invention also provides methods of administering quinupristin/dalfopristin while minimizing skeletal muscle toxicity by administering a therapeutically effective amount of quinupristin/dalfopristin at a dosage interval that dos not result in muscle toxicity.

Abstract: The invention comprises methods useful within a larger process for identifying compounds and/or designing further compounds with activity to produce a desired phenotype (for example, growth inhibition) in cells whose target cell component is the subject of certain studies to identify such compounds. The invention employs constructed cells comprising a regulable gene encoding a biomolecule which modulates (inhibits or activates) in vivo the function of a target component of the cell which can be an enzyme for example. The process incorporates methods for identifying biomolecules that bind to a chosen target cell component in vitro, methods for identifying biomolecules that also bind to the chosen target and modulate its function intracellularly, causing a phenotypic effect.

Abstract: The invention comprises methods useful within a larger process for identifying compounds and/or designing further compounds with activity to produce a desired phenotype (for example, growth inhibition) in cells whose target cell component is the subject of certain studies to identify such compounds. The invention employs constructed cells comprising a regulable gene encoding a biomolecule which modulates (inhibits or activates) in vivo the function of a target component of the cell which can be an enzyme, for example, methionyl-tRNA synthetase of Staphylococcus aureus. The process incorporates methods for identifying biomolecules that bind to a chosen target cell component in vitro, methods for identifying biomolecules that also bind to the chosen target and modulate its function intracellularly, causing a phenotypic effect.

Abstract: A system has been constructed which is suitable for tetracycline-inducible gene expression in Gram-positive bacteria such as Staphylococcus aureus and Bacillus subtilis. The replicon/host gene expression system is tightly regulated, can be used in complex as well as minimal media, and can produce a high level of gene expression upon induction, with a variety of gene products. The gene expression system is suitable for production of products toxic to the host cells, and can be used, for example, for the analysis of gene expression and gene products in Gram-positive bacteria, and in a test of the effect of a peptide or polypeptide inhibitor of an S. aureus enzyme on the growth of S. aureus cells in culture or during infection of an animal.

Abstract: The invention comprises methods useful within a larger process for identifying compounds and/or designing further compounds with activity to produce a desired phenotype (for example, growth inhibition) in cells whose target cell component is the subject of certain studies to identify such compounds. The invention employs constructed cells comprising a regulable gene encoding a biomolecule which modulates (inhibits or activates) in vivo the function of a target component of the cell which can be an enzyme, for example, methionyl-tRNA synthetase of Staphylococcus aureus. The process incorporates methods for identifying biomolecules that bind to a chosen target cell component in vitro, methods for identifying biomolecules that also bind to the chosen target and modulate its function intracellularly, causing a phenotypic effect.

Abstract: The invention provides methods for administering a therapeutically effective amount of daptomycin while minimizing skeletal muscle toxicity. The methods provide daptomycin administration at a dosing interval of 24 hours or greater. This long dosing interval minimizes skeletal muscle toxicity and allows for higher peak concentrations of daptomycin, which is related to daptomycin's efficacy. The invention also provides methods of administering lipopeptide antibiotics other than daptomycin while minimizing skeletal muscle toxicity by administering a therapeutically effective amount of the lipopeptide antibiotic at a dosage interval that does not result in muscle toxicity. The invention also provides methods of administering quinupristin/dalfopristin while minimizing skeletal muscle toxicity by administering a therapeutically effective amount of quinupristin/dalfopristin at a dosage interval that does not result in muscle toxicity.

Abstract: The invention provides methods for administering a therapeutically effective amount of daptomycin while minimizing skeletal muscle toxicity. The methods provide daptomycin administration at a dosing interval of 24 hours or greater. This long dosing interval minimizes skeletal muscle toxicity and allows for higher peak concentrations of daptomycin, which is related to daptomycin's efficacy The invention also provides methods of administering lipopeptide antibiotics other than daptomycin while minimizing skeletal muscle toxicity by administering a therapeutically effective amount of the lipopeptide antibiotic at a dosage interval that does not result in muscle toxicity. The invention also provides methods of administering quinupristin/dalfopristin while minimizing skeletal muscle toxicity by administering a therapeutically effective amount of quinupristin/dalfopristin at a dosage interval that dos not result in muscle toxicity.

Abstract: A system has been constructed which is suitable for tetracycline-inducible gene expression in Gram-positive bacteria such as Staphylococcus aureus and Bacillus subtilis. The replicon/host gene expression system is tightly regulated, can be used in complex as well as minimal media, and can produce a high level of gene expression upon induction, with a variety of gene products. The gene expression system is suitable for production of products toxic to the host cells, and can be used, for example, for the analysis of gene expression and gene products in Gram-positive bacteria, and in a test of the effect of a peptide or polypeptide inhibitor of an S. aureus enzyme on the growth of S. aureus cells in culture or during infection of an animal.

Abstract: This invention is directed to the elucidation of DNA sequences encoding Class B beta-lactamase enzymes from Bacteroides fragilis and the amino acid sequences of those enzymes. This invention is also directed to screening methods for identifying antibiotics which are resistant to such beta-lactamase enzymes or for identifying compounds which inactivate such beta-lactamase enzymes.

Abstract: This invention is directed to the elucidation of DNA sequences encoding Class B beta-lactamase enzymes from Bacteroides fragilis and the amino acid sequences of those enzymes. This invention is also directed to screening methods for identifying antibiotics which are resistant to such beta-lactamase enzymes or for identifying compounds which inactivate such beta-lactamase enzymes.

Abstract: This invention is directed to the elucidation of DNA sequences encoding Class B beta-lactamase enzymes from Bacteroides fragilis and the amino acid sequences of those enzymes. This invention is also directed to screening methods for identifying antibiotics which are resistant to such beta-lactamase enzymes or for identifying compounds which inactivate such beta-lactamase enzymes.