Methods and compositions for regulating biofilm development

Abstract

The present disclosure relates to methods for promoting dispersal of, or preventing formation of microbial biofilms, including: exposing a biofilm to an effective amount of nitric oxide or at least one nitric oxide generating or releasing agent; treating a surface or medium susceptible to biofilm formation with an effective amount of nitric oxide or at least one nitric oxide generating or releasing agent; incorporating an effective amount of nitric oxide or at least one nitric oxide generating or releasing agent in a surface or medium susceptible to biofilm formation; or inducing the accumulation of one or more reactive oxygen or nitrogen species within microorganisms within said biofilm or capable of forming a biofilm. The disclosure also relates to methods for maintaining or enhancing or maintaining and enhancing the functioning of a biofilm, comprising exposing a biofilm to at least one nitric oxide scavenger, at least one antioxidant or at least one nitric oxide scavenger and at least one antioxidant. The disclosure also relates to compositions for promoting dispersal of, or preventing formation of microbial biofilms, or for maintaining or enhancing or maintaining and enhancing the functioning of microbial biofilms.

We claim: 
     
         1 . A method for promoting dispersal of, or preventing formation of a microbial biofilm, the method comprising:
 exposing said biofilm to an effective amount of nitric oxide or at least one nitric oxide generating or releasing agent;   treating a surface or medium susceptible to biofilm formation with an effective amount of nitric oxide or at least one nitric oxide generating or releasing agent;   incorporating an effective amount of nitric oxide or at least one nitric oxide generating or releasing agent in a surface or medium susceptible to biofilm formation; or   inducing the accumulation of an effective amount of one or more reactive oxygen or nitrogen species within microorganisms within said biofilm or capable of forming a biofilm.   
     
     
         2 . The method of  claim 1  wherein the at least one nitric oxide generating or releasing agent comprises one or more nitric oxide donors. 
     
     
         3 . The method of  claim 2  wherein the at least one nitric oxide donor is sodium nitroprusside, S-nitroso-L-glutathione, S-nitroso-N-acetylpenicillamine or a combination thereof. 
     
     
         4 . The method of  claim 1  wherein the microorganisms present in the biofilm or capable of forming a biofilm are of a single species. 
     
     
         5 . The method of  claim 1  wherein the microorganisms present in the biofilm or capable of forming a biofilm are of multiple species. 
     
     
         6 . The method of  claim 1 , wherein the microorganisms within said biofilm or capable of forming a biofilm comprise bacterial or fungal species. 
     
     
         7 . The method of  claim 1 , wherein the microorganisms within said biofilm or capable of forming a biofilm comprise one or more species selected from  Candida  spp.,  Hormoconis  spp.,  Pseudomonas  spp.,  Pseudoalteromonas  spp.,  Staphylococcus  spp.,  Streptococcus  spp.,  Shigella  spp.,  Mycobacterium  spp.,  Enterococcus  spp.,  Escherichia  spp.,  Salmonella  spp.,  Legionella  spp.,  Haemophilus  spp.,  Bacillus  spp.,  Desulfovibrio  spp.,  Shewanella  spp.,  Geobacter  spp.,  Klebsiella  spp.,  Proteus  spp.,  Aeromonas  spp.,  Arthrobacter  spp.,  Micrococcus  spp.,  Serratia  spp.,  Porphyromonas  spp.,  Fusobacterium  spp. and  Vibrio  spp.. 
     
     
         8 . The method of  claim 1 , wherein the microorganisms within said biofilm or capable of forming a biofilm comprise one or species selected from  P. aeruginosa, Staphylococcus epidprmidis, Escherichia coli, Bacillus licheniformis, Serratia marcescens, Fusobacterium nucleatum, Vibrio Cholerae , and  Candida albicans.    
     
     
         9 . The method of  claim 1 , further comprising treating said surface or medium with, incorporating in said surface or medium, or exposing the microorganisms within said biofilm or capable of forming a biofilm to, at least one antimicrobial agent. 
     
     
         10 . The method of  claim 9  wherein the antimicrobial agent is selected from an antibiotic, a surfactant, an oxidative stress-inducing agent, or a combination thereof. 
     
     
         11 . The method of  claim 1  wherein the one or more reactive oxygen or nitrogen species are selected from peroxynitrite, nitric oxide, hydrogen peroxide and superoxide radicals, or a combination thereof. 
     
     
         12 . The method of  claim 1  wherein said method comprises inducing differentiation events in microorganisms within said biofilm which lead to dispersal or wherein said method comprises preventing induction of differentiation events in microorganisms which lead to biofilm formation. 
     
     
         13 . The method of  claim 1  which comprises increasing the sensitivity of a microorganism to one or more antimicrobial agents. 
     
     
         14 . The method of  claim 1 , wherein the effective amount comprises a concentration of at least one nitric oxide generating or releasing agent of from about 1 nM to about 10 mM. 
     
     
         15 . The method of  claim 1 , wherein the effective amount comprises a concentration of at least one nitric oxide generating or releasing agent of from about 10 nM to about 5 μM. 
     
     
         16 . The method of  claim 1 , wherein the effective amount comprises a concentration of at least one nitric oxide generating or releasing agent of from about 10 nM to about 1 μM. 
     
     
         17 . The method of  claim 1  comprising administering to a subject an effective amount of nitric oxide or at least one nitric oxide generating or releasing agent for the treatment or prevention of a biofilm-associated condition in said subject. 
     
     
         18 . The method of  claim 17  further comprising administering to said subject at least one antimicrobial agent.