Antimicrobial compounds
AssigneeTrustees of Tufts College
InventorsStuart B. Levy, Laura M. McMurry
Life of this patent
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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.
Claims100
A method for identifying an antimicrobial compound which interacts with an enoyl ACP reductase (ER) polypeptide, comprising;
- contacting the ER polypeptide with a compound under conditions which allow interaction of the compound with the ER polypeptide to occur;
- and
- detecting the presence or absence of interaction of the compound with the ER polypeptide as an indication of whether the compound is an antimicrobial compound.
A method for identifying an antimicrobial compound, comprising;
- contacting an enoyl reductase molecule with a compound under conditions which allows enzyme activity to occur;
- and
- detecting the presence or absence of enzyme activity as an indication of whether the compound is an antimicrobial compound.
A method for identifying an antimicrobial compound, comprising;
- exposing a microorganism to a compound under conditions which allow fatty acid biosynthesis to occur;
- and
- detecting the inhibition of fatty biosynthesis as an indication of whether the compound is an antimicrobial compound.
A method for identifying an antimicrobial compound which interacts with a mutant ER polypeptide, comprising;
- contacting the mutant ER polypeptide with a compound under conditions which allow interaction of the compound to the mutant ER polypeptide to occur;
- and
- detecting the presence or absence of interaction with the mutant ER polypeptide as an indication of whether the compound is an antimicrobial compound.
A method for identifying an antimicrobial compound capable of inhibiting proliferation or viability of a triclosan-resistant microbial cell, comprising
- contacting a triclosan-resistant microbial cell with a compound under conditions which allow a triclosan-resistant microbial cell to proliferate or remain viable;
- determining whether the compound is capable of inhibiting proliferation or viability of the cell thereby identifying an antimicrobial compound capable of inhibiting proliferation or viability of a triclosan-resistant microbial cell.
A method for identifying an antimicrobial compound capable of inhibiting proliferation or viability of a triclosan-resistant microbial cell, comprising;
- contacting a polypeptide capable of conferring resistance to triclosan with a compound under conditions which allow interaction of the compound to the polypeptide to occur;
- and
- detecting the presence or absence of interaction with the polypeptide as an indication of whether the compound is an antimicrobial compound capable of inhibiting proliferation or viability of a triclosan-resistant microbial cell.
A method for identifying an antimicrobial compound capable of inhibiting proliferation or viability of a NSAM-resistant microbial cell, comprising;
- contacting a polypeptide capable of conferring resistance to a NSAM with a compound under conditions which allows interaction of the compound with the polypeptide to occur;
- and
- detecting the presence or absence of interaction with the polypeptide as an indication of whether the compound is an antimicrobial compound capable of inhibiting proliferation or viability of a NSAM-resistant microbial cell.
A method for identifying an antimicrobial compound capable of inhibiting proliferation or viability of a NSAM-resistant microbial cell, comprising
- contacting a a NSAM-resistant microbial cell with a compound under conditions which allow a a NSAM-resistant microbial cell to proliferate or remain viable;
- determining whether the compound is capable of inhibiting proliferation or viability of the cell thereby identifying an antimicrobial compound capable of inhibiting proliferation or viability of a a NSAM-resistant microbial cell.
A combination product comprising a structural analog of triclosan and a product forming a combination product.
A combination product comprising a structural analog of an NSAM and a product forming a combination product.
An isolated polypeptide capable of conferring resistance to a NSAM in a microbial cell.
An isolated polypeptide capable of conferring resistance to triclosan in a microbial cell.
An isolated mutant ER polypeptide capable of conferring resistance to triclosan in a microbial cell.
A method for treating a subject having growth of an unwanted microorganism with a NSAM, comprising:
- administering to the subject an effective amount of the NSAM such that the subject is treated for the unwanted microorganism.
A method for treating a subject having growth of an unwanted microorganism with a triclosan compound, comprising:
- administering to the subject an effective amount of the triclosan compound such that the subject is treated for the unwanted microorganism.
An antimicrobial soap or detergent preparation comprising triclosan at a concentration of less than about 500 μg per milliliter of soap or detergent preparation forming an antimicrobial soap or detergent preparation.
An antimicrobial soap or detergent preparation comprising a structural analog of triclosan in a soap or detergent preparation forming an antimicrobial soap or detergent preparation, said structural analog of triclosan capable of inhibiting the proliferation and viability of a triclosan-resistant microbial cell.
A method for screening a library of bacteriophage displaying on their surface a plurality of polypeptide sequences, each said polypeptide sequence being encoded by a nucleic acid contained within the bacteriophage, for ability to bind an immobilized ER fatty acid enoyl reductase molecule, to obtain those polypeptides having affinity for the enoyl reductase, said method comprising
- contacting the immobilized enoyl reductase with a sample of the library of bacteriophage so that the enoyl reductase can interact with the different polypeptide sequences and bind those having affinity for the enoyl reductase to form a set of complexes consisting of immobilized enoyl reductase and bound bacteriophage;
- separating the complexes from free bacteriophage which have not formed the complex;
- contacting the complexes of the enoyl reductase and bound bacteriophage with an agent that dissociates the bound bacteriophage from the complexes;
- and
- isolating the dissociated bacteriophage and obtaining the sequence of the nucleic acid encoding the displayed polypeptide, so that amino acid sequences of displayed polypeptides with affinity for fatty acid enoyl reductase are obtained.
Dependencies are inferred from the claim text.