Compositions and methods to reduce mutagenesis

Abstract

The present invention provides methods and compositions for said inhibition of drug resistance. In one embodiment, said invention provides methods and compositions for said inhibition of antibiotic resistance. The invention generally involves said administration of achaogens, agents that inhibit said mutational process, to inhibit said evolution of drug resistance. Also, described herein are compositions that are suitable for use as achaogens.

1 - 64 . (canceled) 
     
     
         65 . A pharmaceutical composition comprising an agent that inhibits a mutation process in a cell or an organism, and a pharmaceutically acceptable carrier. 
     
     
         66 . The pharmaceutical composition of  claim 65 , wherein the mutation process is an SOS response pathway. 
     
     
         67 . The pharmaceutical composition of  claim 65 , wherein said agent inhibits a protein selected from the group consisting of: RecA, RecB, RecC, RecD, RecF, RecG, Rec N, LexA, UmuC, UmuD, PolB, PolIV, Poly, PriA, RuvA, RuvB, RuvC, UmuC, UmuD, UvrA, UvrB, UvrD, and homologs thereof. 
     
     
         68 . The pharmaceutical composition of  claim 67 , wherein said agent inhibits RecA. 
     
     
         69 . The pharmaceutical composition of  claim 67 , wherein said agent inhibits RecB, RecC, or RecD. 
     
     
         70 . The pharmaceutical composition of  claim 67 , wherein said agent inhibits LexA. 
     
     
         71 . The pharmaceutical composition of  claim 67 , wherein said agent comprises a peptide comprising a LexA cleavage sequence. 
     
     
         72 . The pharmaceutical composition of  claim 71 , wherein said peptide comprises a dipeptide Ala-Ala or a tripeptide Val-Ala-Ala. 
     
     
         73 . The pharmaceutical composition of  claim 67 , wherein said agent is an isolated and purified ClpXP, Lon protease, PsiB, DinI, or a variant or fragment thereof. 
     
     
         74 . The pharmaceutical composition of  claim 67 , wherein said agent reduces the expression of a protein selected from the group consisting of: RecA, RecB, RecC, RecD, RecF, RecG, Rec N, LexA, UmuC, UmuD, PolB, PolIV, Poly, PriA, RuvA, RuvB, RuvC, UmuC, UmuD, UvrA, UvrB, UvrD, and homologs thereof. 
     
     
         75 . The pharmaceutical composition of  claim 74 , wherein the protein is RecA. 
     
     
         76 . The pharmaceutical composition of  claim 74 , wherein the protein is RecB, RecC, or RecD. 
     
     
         77 . The pharmaceutical composition of  claim 74 , wherein the protein is LexA. 
     
     
         78 . The pharmaceutical composition of  claim 67 , wherein said agent is an antibody or antibody fragment that specifically binds to a protein selected from the group consisting of: RecA, RecB, RecC, RecD, RecF, RecG, Rec N, LexA, UmuC, UmuD, PolB, PolIV, Poly, PriA, RuvA, RuvB, RuvC, UmuC, UmuD, UvrA, UvrB, UvrD, and homologs thereof. 
     
     
         79 . The pharmaceutical composition of  claim 65 , further comprising a therapeutic agent selected from the group consisting of an antibiotic agent, an antiviral agent, an antifungal agent, an antiprotozoan agent, and an antineoplastic agent. 
     
     
         80 . The pharmaceutical composition of  claim 79 , wherein said therapeutic agent is an antibiotic. 
     
     
         81 . The pharmaceutical composition of  claim 80 , wherein said antibiotic is an aminoglycoside, a carbapenem, a cephalosporin, a cephem, a glycopeptide, a quinolone, a macrolide, an oxazolidinone, a penicillin, a streptogramin, a sulfonamide, metronidazole, or a tetracycline. 
     
     
         82 . The pharmaceutical composition of  claim 81 , wherein said antibiotic is a quinolone. 
     
     
         83 . The pharmaceutical composition of  claim 81 , wherein said agent inhibits LexA or RecA, and wherein said agent inhibits the evolution of resistance to said quinolone in a bacteria. 
     
     
         84 . A kit comprising a container comprising the pharmaceutical composition of  claim 65 . 
     
     
         85 . The kit of  claim 84 , wherein said pharmaceutical composition further comprises a therapeutic agent selected from the group consisting of: an antibiotic agent, an antiviral agent, an antifungal agent, an antiprotozoan agent, and an antineoplastic agent. 
     
     
         86 . The kit of  claim 84 , wherein said kit comprises a second container comprising a therapeutic agent selected from the group consisting of: an antibiotic agent, an antiviral agent, an antifungal agent, an antiprotozoan agent, and an antineoplastic agent. 
     
     
         87 . The kit of  claim 86 , wherein the agent inhibits LexA or RecA and said therapeutic agent is a quinolone. 
     
     
         88 . The kit of  claim 84 , wherein the agent inhibits LexA or RecA and said therapeutic agent is a quinolone.