Rapid drug discovery methods for pathogen inactivation

Abstract

Provided herein are rapid, large-scale screening methods for identifying metal-biocide combinations that are synergistically effective to kill or inhibit the growth of microorganisms. Also provided herein are novel, synergistically antimicrobial metal-biocide combinations and uses of such compositions to curb or slow microbial growth.

1 . An antimicrobial composition comprising: (a) a biocide; and (b) a Group IB metal; wherein the composition has a coefficient of drug interaction (CDI) less than or equal to 0.5, wherein the CDI is calculated as (A+B)/A×B, wherein A is growth in the presence of the culture medium comprising the soluble Group D3 metal but lacking the test biocide normalized to growth in LB medium, B is growth in a same culture medium comprising the test biocide but lacking the Group IB metal normalized to growth in LB medium, and A×B is growth in the culture medium comprising the soluble Group IB metal and the test biocide normalized to growth in LB medium. 
     
     
         2 . The antimicrobial composition of  claim 1 , wherein the metal is gold and the biocide is disulfiram, thiosalisylic acid, novobiocin, chlorpromazine, or a biocide selected from the group consisting of a glycopeptide, a macrolide, and a sodium channel inhibitor. 
     
     
         3 . The antimicrobial composition of  claim 2 , wherein the glycopeptide is selected from bleomycin and vancomycin. 
     
     
         4 . The antimicrobial composition of  claim 2 , wherein the macrolide is selected from the group consisting of erythromycin, josamycin, oleandomycin, spiramycin, troleandomycin, and tylosin. 
     
     
         5 . The antimicrobial composition of  claim 2 , wherein the sodium channel inhibitor is lidocaine or procaine. 
     
     
         6 . The antimicrobial composition of  claim 1 , wherein the metal is silver and the biocide is selected from the group consisting of 5,7-dichloro-8-hydroxyquinaldine, 5,7-dichloro-8-hydroxyquinoline, 5-chloro-7-iodo-8-hydroxyquinoline, 8-hydroxyquinoline, 9-aminoacridine, acriflavine, novobiocin, proflavine, nordihydroguaiaretic acid, dichlofluanid, tolylfluanid, lidocaine, procaine, D,L-serine hydroxamate, D,L-methionine hydroxamate, L-glutamic-γ-hydroxamate, erythromycin, josamycin, oleandomycin, troleandomycin, tylosin, benserazide, chlorpromazine, promethazine, thioridazine, trifluoperazine, dodine, guanidine hydrochloride, atropine, orphenadrine, 2-nitroimidazole, ornidazole, methyl viologen, D,L-propanolol, patulin, sanguinarine, and iodoacetate. 
     
     
         7 . The antimicrobial composition of  claim 1 , wherein the metal is copper and the biocide is selected from the group consisting of chlorodinitrobenzene, methyl viologen, thioctic acid, iodonitrotetrazolium violet, fusidic acid, nordihydroguaiaretic acid, a nitrofuran, a triazole, a fenicol, lauryl sulfobetaine, niaproof, menadione, and lidocaine. 
     
     
         8 . A method of killing a microorganism or inhibiting its growth by the application of an effective amount of an antimicrobial composition according to  claim 1 . 
     
     
         9 . The method of  claim 8 , wherein the microorganism is a bacterium. 
     
     
         10 . A method for inhibiting microbiological growth on or in an object which comprises contacting an antimicrobial composition according to  claim 1  to the object. 
     
     
         11 . The method of  claim 10 , wherein the object is a medical device. 
     
     
         12 . The method of  claim 10 , whereby growth of one or more types of microorganisms on the contacted object is inhibited. 
     
     
         13 - 18 . (canceled)