Abstract: The present invention relates to novel cephalosporin antibiotics, prodrugs thereof and pharmacologically acceptable salts of either, which are active against a wide spectrum of bacteria that are resistant to present clinical beta-lactam antibiotics.

Abstract: Compounds are described which have efflux pump inhibitor activity. Also described are methods of using such efflux pump inhibitor compounds and pharmaceutical compositions which include such compounds.

Abstract: Methods of screening for antimicrobial agents or other compounds active on a particular strain are described. These methods use pools of strains of cells or microbes in order to screen for activity on many cellular targets in a single screen. The strain or strains in the pool for which growth is inhibited or stimulated are determined; such identification can also provide a means of identifying the cellular target on which a compound is active.

Abstract: Compounds are described which have efflux pump inhibitor activity. Also described are methods of using such efflux pump inhibitor compounds and pharmaceutical compositions which include such compounds.

Abstract: This disclosure describes isolated or purified deoxyribonucleotide (DNA) sequences, useful for the development of antibacterial agents, which contain the coding sequences of bacterial pathogenesis genes or essential genes, which are expressed in vivo. It further describes isolated or purified DNA sequences which are portions of such bacterial genes, which are useful as probes to identify the presence of the corresponding gene or the presence of a bacteria containing that gene. Also described are hypersensitive mutant cells containing a mutant gene corresponding to any of the identified sequences and methods of screening for antibacterial agents using such hypersensitive cells. In addition it describes methods of treating bacterial infections by administering an antibacterial agent active against one of the identified targets, as well as pharmaceutical compositions effective in such treatments.

Abstract: The invention provides novel antibiotics of the pacidamycin group of uridyl peptide antibiotics and methods of preparing and using those compounds.

Abstract: Compounds are described which have efflux pump inhibitor activity. Also described are methods of using such efflux pump inhibitor compounds and pharmaceutical compositions which include such compounds.

Abstract: This disclosure describes isolated or purified deoxyribonucleotide (DNA) sequences, useful for the development of antibacterial agents, which contain the coding sequences of bacterial pathogenesis genes or essential genes, which are expressed in vivo. It further describes isolated or purified DNA sequences which are portions of such bacterial genes, which are useful as probes to identify the presence of the corresponding gene or the presence of a bacteria containing that gene. Also described are hypersensitive mutant cells containing a mutant gene corresponding to any of the identified sequences and methods of screening for antibacterial agents using such hypersensitive cells. In addition it describes methods of treating bacterial infections by administering an antibacterial agent active against one of the identified targets, as well as pharmaceutical compositions effective in such treatments.

Abstract: Compounds are described which have efflux pump inhibitor activity. Also described are methods of using such efflux pump inhibitor compounds and pharmaceutical compositions which include such compounds.

Abstract: The present invention includes novel compounds of formula ##STR1## where A, B, D, and E are selected from the group consisting of carbon, nitrogen and sulfur, R.sup.99 is selected from the group consisting of sulfur, SO, SO.sub.2, NH, N-alkyl, oxygen, C.dbd.C (cis or trans), and C.tbd.C, and R.sup.12 is NR.sup.13 R.sup.14, ##STR2## The invention also includes the pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to .beta.-lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounds of the present invention and to novel methods for producing the novel compounds and intermediate compounds.

Abstract: The present invention includes novel compounds of formula ##STR1## where R.sup.99 is selected from the group consisting of sulfur, SO, SO.sub.2, NH, N-alkyl, oxygen, C.dbd.C (cis or trans), and C.tbd.C, and R.sup.12 is ##STR2## The invention also includes the pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to .beta.-lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounds of the present invention and to novel methods for producing the novel compounds and intermediate compounds.

Abstract: The present invention includes novel compounds of formula ##STR1## where G, H, J, L and M are carbon or nitrogen, R.sup.99 is selected from the group consisting of sulfur, SO, SO.sub.2, NH, N-alkyl, oxygen, C.dbd.C (cis or trans), and C.tbd.C, and R.sup.12 is NR.sup.13 R.sup.14, ##STR2## The invention also includes the pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to .beta.-lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounds of the present invention and to novel methods for producing the novel compounds and intermediate compounds.

Abstract: This disclosure describes isolated or purified deoxyribonucleotide (DNA) sequences, useful for the development of antibacterial agents, which contain the coding sequences of bacterial pathogenesis genes or essential genes, which are expressed in vivo. It further describes isolated or purified DNA sequences which are portions of such bacterial genes, which are useful as probes to identify the presence of the corresponding gene or the presence of a bacteria containing that gene. Also described are hypersensitive mutant cells containing a mutant gene corresponding to any of the identified sequences and methods of screening for antibacterial agents using such hypersensitive cells. In addition it describes methods of treating bacterial infections by administering an antibacterial agent active against one of the identified targets, as well as pharmaceutical compositions effective in such treatments.

Abstract: The present invention includes novel compounds of formula where A, B, D, and E are selected from the group consisting of carbon, nitrogen and sulfur, R.sup.99 is selected from the group consisting of sulfur, SO, S0.sub.2, NH, N-alkyl, oxygen, C.dbd.C (cis or trans), and C.tbd.C, and R.sup.12 is NR.sup.13 R.sup.14, ##STR1## The invention also includes the pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to .beta.-lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounds of the present invention and to novel methods for producing the novel compounds and intermediate compounds.

Abstract: The present invention includes novel compounds of formula ##STR1## where G, H, J, L and M are carbon or nitrogen, R.sup.99 is selected from the group consisting of sulfur, SO, SO.sub.2, NH, N-alkyl, oxygen, C.tbd.C (cis or trans), and C.tbd.C, and R.sup.12 is NR.sup.13 R.sup.14, ##STR2## The invention also includes the pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to .beta.-lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounds of the present invention and to novel methods for producing the novel compounds and intermediate compounds.

Abstract: Methods are provided for screening for potential inhibitors of bacterial, or other microbial, global pathogenesis gene regulators and other gene regulators. Methods are also provided for treating microbial (e.g., bacterial) infections using such inhibitors. Also included are pharmaceutical compositions containing such inhibitors. The screening methods involve detecting whether the activity of a global pathogenesis gene regulator is altered in the presence of a test compound.

Abstract: Methods are provided for screening for inhibitors of microbial efflux pumps including those which export antibiotics. The screening methods are based on the increase in the intracellular concentration of a compound, such as an antibiotic, when the bacterial cells are contacted with an efflux pump inhibitor. In addition, this invention provides pharmaceutical compositions containing such efflux pump inhibitors, and methods for treating microbial infections using those compositions.

Abstract: A method for identifying a cell or strain of cells containing a mutation in a gene involved in growth, comprising the steps of forming a labeled set of strains comprising a plurality of members, each member of the set containing an exogenous DNA fragment of a defined length stably integrated into the chromosome of a member, the defined length in each member differing from the defined length in other members, subjecting the labeled set of strains to mutagenesis so as to obtain mutants from each member of the set of strains, and introducing the mutant strains into a growth environment for a period of time sufficient for growth of a non-mutated strain and determining which strains have reduced growth compared to a non-mutated strain, by determining the presence and size of exogenous DNA fragments relative to each other using PCR and agarose/polyacrylamide gel electrophoresis.

Abstract: Methods for screening for compounds which potentiate the activity of antibacterial agents against bacteria resistant to the antibacterial agent alone, pharmaceutical compositions including such potentiators, and methods of treating bacterial infections using a combination of a potentiator and a potentiated antibacterial agent, which are useful for overcoming the resistance of a bacterial strain for an antibacterial agent.

Abstract: The present invention includes novel (7R)-7-(acylamino)-3-(arylthio)-3-cephem-4-carboxylic acids or their pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to .beta.-lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounde of the present invention and to novel methods for producing the novel compounds and intermediate compounds.