Claims
1. A method for identifying a compound capable of modulating a biofilm-related activity, said method comprising:
(a) obtaining supematant from a closed culture system, said system comprising at least one type of a source microorganism;
(b) exposing a target organism to said supernatant or an extract thereof; and
(c) measuring the level of said activity.
2. The method of claim 1, wherein said modulating is inhibition of biofilm formation.
3. The method of claim 1 , wherein said modulating is disruption of a pre-exisiting biofilm.
4. The method of claim 1 , wherein said modulating is promotion of attachment of cells to a surface.
5. The method of claim 1 , wherein said modulating is promotion of biofilm development following attachment to a surface.
6. The method of claim 1, wherein said exposing occurs at the time of inoculation of a culture media with said target organism.
7. The method of claim 1, wherein said exposing occurs after inoculation of a culture medium with said target organism.
8. The method of claim 1, wherein said exposing occurs before said target organism has formed a biofilm. „
9. The method of claim 1 , wherein said target organism has formed a biofilm prior to said exposing.
10. The method of claim 1 , wherein said compound promotes the formation of a biofilm
11. The method of claim 10, wherein said compound promotes attachment of cells to a surface.
12. The method of claim 10, wherein said compound promotes biofilm development following attachment to a surface.
13. The method of claim 1 , wherein said compound inhibits the formation of a biofilm.
14. The method of claim 13, wherein said compound inhibits attachment of cells to a surface.
15. The method of claim 13 , wherein said compound inhibits biofilm development following attachment to a surface.
16. The method of claim 1, wherein said compound dismpts a preexisting biofilm.
17. The method of claim 1, wherein said compound decreases the viability of microorganisms in a biofilm.
18. The method of claim 1 , wherein said compound potentiates the microbiocidal activity of an antibiotic agent or biocide against a microorganism in a biofilm.
19. The method of claim 1 , wherein said source microorganism or said target organism comprises at least one organism selected from the group consisting of archaea, bacteria, fungi, protozoa, and algae.
20. The method of claim 19, wherein said source microorganism or said target organism is a bacterial organism.
21. The method of claim 20, wherein said bacterial organism is selected from the group consisting of Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivalis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio paramaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, Bacteroides spp., Clostridium difficile,
Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actmomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp., Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Desulfosarcina spp., Deslfuromonas spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp., Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp., Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentificans, Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp., Chromobacterium spp., Saccharopolyspora spp., Actinobacillus spp., Alteromonas spp., Aeronomonas spp., Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus and Rhizobium spp., and mutant derivatives thereof.
22. The method of claim 21 , wherein said bacterial organism is
Pseudomonas aeruginosa.
23. The method of claim 21 , wherein said bacterial organism is selected from Streptococcus spp.
24. The method of claim 21 , wherein said bacterial organism is Staphylococcus aureus.
25. The method of claim 21 , wherein said bacterial organism is Staphylococcus epidermis.
26. The method of claim 21, wherein said bacterial organism is selected from Rhizobium spp.
27. The method of claim 19, wherein said source microorganism or said target organism is a fungal organism.
28. The method of claim 27, wherein said fungal organism is selected from the group consisting of Absidia spp., Actinomadura madurae, Actmomyces spp., Allescheria boydii, Alternaria spp., Anthopsis deltoidea, Aphanomyces spp., Apophysomyces eleqans, Armillaria spp., Arnium leoporinum, Aspergillus spp., Aureobasidium pullulans, Basidiobolus ranarum, Bipolaris spp., Blastomyces dermatitidis, Botrytis spp., Candida spp., Centrospora spp., Cephalosporium spp., Ceratocystis spp., Chaetoconidium spp., Chaetomium spp., Cladosporium spp., Coccidioides immitis, Colletotrichum spp, Conidiobolus spp., Corynebacterium tenuis, Cryptoporiopsis spp., Cylindrocladium spp., Cryptococcus spp.,
Cunninghamella bertholletiae, Curvularia spp., Dactylaria spp., Diplodia spp., Epidermophyton spp., Epidermophyton floccosum, Exserophilum spp., Exophiala spp., Fonsecaea spp., Fulvia spp., Fusarium spp., Geotrichum spp., Guignardia spp., Helminthosporium spp., Histoplasma spp., Lecythophora spp., Macrophomina spp., Madurella spp., Magnaporthe spp., Malasseziafwfur, Microsporam spp., Monilinia spp., Mucor spp., Mycocentrospora acerina, Nectria spp., Nocardia spp., Oospora spp., Ophiobolus spp., Paecilomyces spp., Paracoccidioides brasiliensis, Penicillium spp., Phaeosclera dematioides, Phaeoannellomyces spp., Phialemonium obovatum, Phialophora spp., Phlyctaena spp., Phoma spp., Phomopsis spp., Phymatotrichum spp., Phytophthora spp., Pythium spp., Piedraia hortai, Pneumocystis carinii, Puccinia spp., Pythium insidiosum, Rhinocladiella aquaspersa, Rhizomucor pusillus, Rhizoctonia spp., Rhizopus spp., Saccharomyces spp., Saksenaea vasiformis, Sarcinomycesphaeomuriformis, Scerotium spp., Sclerotinia spp., Sphaerotheca spp., Sporothrix schenckii, Syncephalastrum racemosum, Taeniolella boppii, Taphrina spp., Thielaviopsis spp., Tomlopsosis spp., Trichophyton spp., Trichosporon spp., Ulocladium chartarum, Ustilago spp., Venturia spp., Verticillium spp., Wangiella dermatitidis, Whetxelinia spp., Xylohypha spp., and their synonyms.
29. The method of claim 28, wherein said fungal organism is selected from Candida spp.
30. The method of claim 1 , wherein said supernatant is spent supernatant obtained from a source microorganism at the stationary phase.
31. The method of claim 1 , wherein said supernatant is obtained from a source microorganism at the exponential phase.
32. The method of claim 31 , wherein said source microorganism is at the early exponential phase.
33. The method of claim 31 , wherein said source microorganism is at the mid exponential phase.
34. The method of claim 31 , wherein said source microorganism is at the late exponential phase.
35. The method of claim 1 , wherein said source microorganism of said closed culture system is grown on a surface.
36. The method of claim 1 , wherein said source microorganism of said closed culture system is grown planktonically.
37. The method of claim 1 , wherein said source microorganism of said closed culture system is grown planktonically and on a surface.
38. The method of claim 1, wherein said source microorganism is different from said target organism.
39. The method of claim 1, wherein said source microorganism is the same as said target organism.
40. The method of claim 1 , wherein said method comprises at least two closed culture systems, each of said culture systems having a different strain of microorganism and wherein said target organism is exposed to the supernatant of each of said culture systems.
41. The method of claim 1, wherein said culture system comprises more than one type of microorganism.
42. The method of claim 1, wherein said culture system is a pure culture system comprising only one strain of microorganism.
43. The method of claim 1 , wherein said method comprises at least two closed culture systems, each of said culture systems having a different set of culture conditions.
44. The method of claim 1, wherein said target organism comprises more than one type of microorganism.
45. A method for preventing a target organism from participating in formation of a biofilm, said method comprising exposing said target organism to supernatant from a closed culture system or an extract thereof.
46. The method of claim 45, wherein said target organism comprises at least one organism selected from the group consisting of archaea, bacteria, fungi, protozoa, and algae.
47. The method of claim 46, wherein said target organism is a bacterial organism.
48. The method of claim 47, wherein said bacterial organism is selected from the group consisting of Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivalis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica,
Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter ejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio paramaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, Bacteroides spp., Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actinomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp.,
Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Desulfosarcina spp., Deslfuromonas spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp., Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp., Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentificans, Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp., Chromobacterium spp., Saccharopolyspora spp., Actinobacillus spp., Alteromonas spp., Aeronomonas spp., Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus and Rhizobium spp. , and mutant derivatives thereof.
49. The method of claim 48, wherein said bacterial organism is Pseudomonas aeruginosa.
50. The method of claim 48, wherein said bacterial organism is selected from Streptococcus spp.
51. The method of claim 48, wherein said bacterial organism is Staphylococcus aureus.
52. The method of claim 48, wherein said bacterial organism is
Staphylococcus epidermis.
53. The method of claim 46, wherein said target organism is a fungal organism.
54. The method of claim 53, wherein said fungal organism is selected from the group consisting of Absidia spp., Actinomadura madurae, Actinomyces spp., Allescheria boydii, Altemaria spp., Anthopsis deltoidea, Aphanomyces spp., Apophysomyces eleqans, Armillaria spp., Arnium leoporinum, Aspergillus spp., Aureobasidium pullulans, Basidiobolus ranarum, Bipolaris spp., Blastomyces dermatitidis, Botrytis spp., Candida spp., Centrospora spp., Cephalosporium spp., Ceratocystis spp., Chaetoconidium spp., Chaetomium spp., Cladosporium spp., Coccidioides immitis, Colletotrichum spp, Conidiobolus spp., Corynebacterium tenuis, Cryptoporiopsis spp., Cylindrocladium spp., Cryptococcus spp., Cunninghamella bertholletiae, Curvularia spp., Dactylaria spp., Diplodia spp., Epidermophyton spp., Epidermophyton floccosum, Exserophilum spp., Exophiala spp., Fonsecaea spp., Fulvia spp., Fusarium spp., Geotrichum spp., Guignardia spp., Helminthosporium spp., Histoplasma spp., Lecythophora spp., Macrophomina spp., Madurella spp., Magnaporthe spp., Malasseziafwfur, Microsporam spp., Monilinia spp., Mucor spp., Mycocentrospora acerina, Nectria spp., Nocardia spp., Oospora spp., Ophiobolus spp., Paecilomyces spp., Paracoccidioides brasiliensis,
Penicillium spp., Phaeosclera dematioides, Phaeoannellomyces spp., Phialemonium obovatum, Phialophora spp., Phlyctaena spp., Phoma spp., Phomopsis spp., Phymatotrichum spp., Phytophthora spp., Pythium spp., Piedraia hortai, Pneumocystis carinii, Puccinia spp., Pythium insidiosum, Rhinocladiella aquaspersa, Rhizomucor pusillus, Rhizoctonia spp., Rhizopus spp., Saccharomyces spp., Saksenaea vasiformis, Sarcinomyces phaeomuriformis, Scerotium spp., Sclerotinia spp., Sphaerotheca spp., Sporothrix schenckii, Syncephalastrum racemosum, Taeniolella boppii, Taphrina spp., Thielaviopsis spp., Tomlopsosis spp., Trichophyton spp., Trichosporon spp., Ulocladium chartarum, Ustilago spp., Venturia spp., Verticillium spp., Wangiella dermatitidis, Whetxelinia spp., Xylohypha spp., and their synonyms.
55. The method of claim 54, wherein said fungal organism is selected from Candida spp.
56. The method of claim 45, wherein said supernatant is spent supernatant obtained from a source microorganism at the stationary phase.
57. The method of claim 45, wherein said supernatant is obtained from a source microorganism at the exponential phase.
58. The method of claim 57, wherein said source microorganism is at the early exponential phase.
59. The method of claim 57, wherein said source microorganism is at the mid exponential phase. •
60. The method of claim 57, wherein said source microorganism is at the late exponential phase.
61. The method of claim 45, wherein said closed culture system comprises a source microorganism grown on a surface.
62. The method of claim 45, wherein said closed culture system comprises a source microorganism grown planktonically.
63. The method of claim 45, wherein said closed culture system comprises a source microorganism grown planktonically and on a surface.
64. The method of claim 45, wherein said supernatant has been treated to increase the concentration of a biofilm-modulating compound.
65. The method of claim 64, wherein said treatment comprises purification of said supernatant.
66. The method of claim 47, wherein said bacterial organism is a coagulase-negative staphylococcus.
67. A method for disrupting a biofilm, said method comprising exposing said biofilm to a supernatant from a closed culture system or an extract thereof.
68. The method of claim 67, wherein said biofilm comprises at least one target organism selected from the group consisting of archaea, bacteria, fungi, protozoa, and algae.
69. The method of claim 68, wherein said target organism is a bacterial organism
70. The method of claim 69, wherein said bacterial organism is selected from the group consisting of. Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivalis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirάbilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio paramaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, Bacteroides spp., Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcer ans, Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actinomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp., Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Desulfosarcina spp., Deslfuromonas spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp.,
Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp., Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentificans, Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp., Chromobacterium spp., Saccharopolyspora spp., Actinobacillus spp., Alteromonas spp., Aeronomonas spp., Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus and Rhizobium spp. , and mutant derivatives thereof.
71. The method of claim 70, wherein said bacterial organism is Pseudomonas aeruginosa.
72. The method of claim 70, wherein said bacterial organism is selected from Streptococcus spp.
73. The method of claim 70, wherein said bacterial organism is Staphylococcus aureus.
74. The method of claim 70, wherein said bacterial organism is Staphylococcus epidermis.
75. The method of claim 69, wherein said bacterial organism is a coagulase-negative staphylococcus .
76. The method of claim 68, wherein said organism is a fungal organism.
77. The method of claim 76, wherein said fungal organism is selected from the group consisting of Absidia spp., Actinomadura madurae, Actinomyces spp., Allescheria boydii, Alternaria spp., Anthopsis deltoidea, Aphanomyces spp., Apophysomyces eleqans, Armillaria spp., Arnium leoporinum, Aspergillus spp., Aureobasidium pullulans, Basidiobolus ranarum, Bipolaris spp., Blastomyces dermatitidis, Botrytis spp., Candida spp., Centrospora spp., Cephalosporium spp., Ceratocystis spp., Chaetoconidium spp., Chaetomium spp., Cladosporium spp., Coccidioides immitis, Colletotrichum spp, Conidiobolus spp., Corynebacterium tenuis, Cryptoporiopsis spp., Cylindrocladium spp., Cryptococcus spp., Cunninghamella bertholletiae, Curvularia spp., Dactylaria spp., Diplodia spp., Epidermophyton spp., Epidermophyton floccosum, Exserophilum spp., Exophiala spp., Fonsecaea spp., Fulvia spp., Fusarium spp., Geotrichum spp., Guignardia spp., Helminthosporium spp., Histoplasma spp., Lecythophora spp., Macrophomina spp., Madurella spp., Magnaporthe spp., Malasseziafwfur, Microsporam spp., Monilinia spp., Mucor spp., Mycocentrospora acerina, Nectria spp., Nocardia spp., Oospora spp., Ophiobolus spp., Paecilomyces spp., Paracoccidioides brasiliensis, Penicillium spp., Phaeosclera dematioides, Phaeoannellomyces spp., Phialemonium obovatum, Phialophora spp., Phlyctaena spp., Phoma spp., Phomopsis spp., Phymatotrichum spp., Phytophthora spp., Pythium spp., Piedraia hortai, Pneumocystis carinii, Puccinia spp., Pythium insidiosum, Rhinocladiella aquaspersa, Rhizomucor pusillus, Rhizoctonia spp., Rhizopus spp., Saccharomyces spp., Saksenaea vasiformis, Sarcinomycesphaeomuriformis, Scerotium spp., Sclerotinia spp., Sphaerotheca spp., Sporothrix schenckii, Syncephalastrum racemosum, Taeniolella boppii, Taphrina spp., Thielaviopsis spp., Tomlopsosis spp., Trichophyton spp., Trichosporon spp., Ulocladium chartarum, Ustilago spp., Venturia spp., Verticillium spp., Wangiella dermatitidis, Whetxelinia spp., Xylohypha spp., and their synonyms.
78. The method of claim 77, wherein said fungal species is selected from Candida spp.
79. The method of claim 67, wherein said supernatant is spent supernatant obtained from a source microorganism at the stationary phase.
80. The method of claim 67, wherein said supernatant is obtained from a source microorganism at the exponential phase.
81. The method of claim 80, wherein said source microorganism is at the early exponential phase.
82. The method of claim 80, wherein said source microorganism is at the mid exponential phase.
83. The method of claim 80, wherein said source microorganism is at the late exponential phase.
84. The method of claim 67, wherein said closed culture system comprises a source microorganism grown on a surface.
85. The method of claim 67, wherein said closed culture system comprises a source microorganism grown planktonically.
86. The method of claim 67, werhein said closed culture system comprises a source microorganism grown on a surface and planktonically.
87. The method of claim 67, wherein said supernatant has been treated to increase the concentration of a biofilm-modulating compound.
88. The method of claim 87, wherein said treatnent comprises purification of said supernatant.
89. A method for promoting the formation of a biofilm, said method comprising exposing said biofilm to the supernatant of a closed culture system or an extract thereof.
90. The method of claim 89, wherein said biofilm comprises at least one target organism selected from the group consisting of archaea, bacteria, fungi, protozoa and algae.
91. The method of claim 90, wherein said target organism is a bacterial organism.
92. The method of claim 91 , wherein said bacterial organism is selected from the group consisting of Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivalis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio paramaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, Bacteroides spp., Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actinomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp., Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Desulfosarcina spp., Deslfuromonas spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp., Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp., Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentificans, Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp., Chromobacterium spp., Saccharopolyspora spp., Actinobacillus spp., Alteromonas spp., Aeronomonas spp., Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus and Rhizobium spp. , and mutant derivatives thereof.
93. The method of claim 92, wherein said bacterial organism is
Pseudomonas aeruginosa.
94. The method of claim 92, wherein said bacterial organism is selected from Streptococcus spp.
95. The method of claim 92, wherein said bacterial organism is Staphylococcus aureus.
96. The method of claim 92, wherein said bacterial organism is Staphylococcus epidermis.
97. The method of claim 91, wherein said bacterial organism is a coagulase-negative Stop hylococcus.
98. The method of claim 90, wherein said target organism is a fungal organism.
99. The method of claim 98, wherein said fungal organism is selected from the group consisting of Absidia spp., Actinomadura madurae, Actinomyces spp., Allescheria boydii, Alternaria spp., Anthopsis deltoidea, Aphanomyces spp., Apophysomyces eleqans, Armillaria spp., Arnium leoporinum, Aspergillus spp., Aureobasidium pullulans, Basidiobolus ranarum, Bipolaris spp., Blastomyces dermatitidis, Botrytis spp., Candida spp., Centrospora spp., Cephalosporium spp., Ceratocystis spp., Chaetoconidium spp., Chaetomium spp., Cladosporium spp., Coccidioides immitis, CoUetotrichum spp, Conidiobolus spp., Corynebacterium tenuis, Cryptoporiopsis spp., Cylindrocladium spp., Cryptococcus spp., Cunninghamella bertholletiae, Curvularia spp., Dactylaria spp., Diplodia spp., Epidermophyton spp., Epidermophyton floccosum, Exserophilum spp., Exophiala spp., Fonsecaea spp., Fulvia spp., Fusarium spp., Geotrichum spp., Guignardia spp., Helminthosporium spp., Histoplasma spp., Lecythophora spp., Macrophomina spp., Madurella spp., Magnaporthe spp., Malasseziafwfur, Microsporam spp., Monilinia spp., Mucor spp., Mycocentrospora acerina, Nectria spp., Nocardia spp., Oospora spp., Ophiobolus spp., Paecilomyces spp., Paracoccidioides brasiliensis, Penicillium spp., Phaeosclera dematioides, Phaeoannellomyces spp., Phialemonium obovatum, Phialophora spp., Phlyctaena spp., Phoma spp., Phomopsis spp., Phymatotrichum spp., Phytophthora spp., Pythium spp., Piedraia hortai, Pneumocystis carinii, Puccinia spp., Pythium insidiosum, Rhinocladiella aquaspersa, Rhizomucor pusillus , Rhizoctonia spp., Rhizopus spp., Saccharomyces spp., Saksenaea vasiformis, Sarcinomycesphaeomuriformis, Scerotium spp., Sclerotinia spp., Sphaerotheca spp., Sporothrix schenckii, Syncephalastrum racemosum, Taeniolella boppii, Taphrina spp., Thielaviopsis spp., Tomlopsosis spp., Trichophyton spp., Trichosporon spp., Ulocladium chartarum, Ustilago spp., Venturia spp., Verticillium spp., Wangiella dermatitidis, Whetxelinia spp., Xylohypha spp., and their synonyms.
100. The method of claim 99, wherein said fungal organism is selected from Candida spp.
101. The method of claim 89, wherein said supernatant is spent supernatant obtained from a source microorganism at the stationary phase.
102. The method of claim 89, wherein said supernatant is obtained from a source microorganism at the exponential phase.
103. The method of claim 102, wherein said source microorganism is at the early exponential phase.
104. The method of claim 102, wherein said source microorganism is at the mid exponential phase.
105. The method of claim 102, wherein said source microorganisms is at the late exponential phase.
106. The method of claim 89, wherein said closed culture system comprises a source microorganism grown on a surface.
107. The method of claim 89, wherein said closed culture system comprises a source microorganism grown planktonically.
108. The method of claim 89, wherein said closed culture system comprises a source microorganism grown planktonically and on a surface.
109. The method of claim 89, wherein said supernatant has been treated to increase the concentration of a biofilm-modulating compound.
110. The method of claim 109, wherein said treatment comprises purification of said supernatant
111. Method for decreasing the viability of a microorganism within a biofilm said method comprising exposing said microorganism to the supernatant of a closed culture system or an extract thereof.
112. The method of claim 111, wherein said biofilm comprises at least one target organism selected from the group consisting of achaea, bacteria, fungi, protozoa, and algae.
113. The method of claim 112, wherein said organism is a bacterial organism.
114. The method of claim 113, wherein said bacterial organism is selected from the group consisting of Pseudomonas fluorescens, Pseudomonas aeruginosa,
Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivalis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio paramaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, Bacteroides spp., Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actinomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp., Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Desulfosarcina spp., Deslfuromonas spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp., Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp., Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentiflcans, Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp.,
Chromobacterium spp., Saccharopolyspora spp., Actinobacillus spp., Alteromonas spp., Aeronomonas spp., Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus and Rhizobium spp. , and mutant derivatives thereof.
115. The method of claim 114, wherein said bacterial organism is Pseudomonas aeruginosa.
116. The method of claim 114, wherein said bacterial organism is selected from Streptococcus spp.
117. The method of claim 114, wherein said bacterial organism is
Staphylococcus aureus.
118. The method of claim 114, wherein said bacterial organism is Staphylococcus epidermis.
119. The method of claim 113, wherein said bacterial organism is a coagulase-negative Staphylococcus.
120. The method of claim 112, wherein said target organism is a fungal organism.
121. The method of claim 120, wherein said fungal organism is selected from the group consisting of Absidia spp., Actinomadura madurae, Actinomyces spp., Allescheria boydii, Alternaria spp., Anthopsis deltoidea, Aphanomyces spp., Apophysomyces eleqans, Armillaria spp., Amium leoporinum, AspergiUus spp., Aureobasidium pullulans, Basidiobolus ranarum, Bipolaris spp., Blastomyces dermatitidis, Botrytis spp., Candida spp., Centrospora spp., Cephalosporium spp., Ceratocystis spp., Chaetoconidium spp., Chaetomium spp., Cladosporium spp., Coccidioides immitis, CoUetotrichum spp, Conidiobolus spp., Corynebacterium tenuis, Cryptoporiopsis spp., Cylindrocladium spp., Cryptococcus spp.,
Cunninghamella bertholletiae, Curvularia spp., Dactylaria spp., Diplodia spp., Epidermophyton spp., Epidermophyton floccosum, Exserophilum spp., Exophiala spp., Fonsecaea spp., Fulvia spp., Fusarium spp., Geotrichum spp., Guignardia spp., Helminthosporium spp., Histoplasma spp., Lecythophora spp., Macrophomina spp., Madurella spp., Magnaporthe spp., Malassezia furfur, Microsporam spp., Monilinia spp., Mucor spp., Mycocentrospora acerina, Nectria spp., Nocardia spp., Oospora spp., Ophiobolus spp., Paecilomyces spp., Paracoccidioides brasiliensis, Penicillium spp., Phaeosclera dematioides, Phaeoannellomyces spp., Phialemonium obovatum, Phialophora spp., Phlyctaena spp., Phoma spp., Phomopsis spp., Phymatotrichum spp., Phytophthora spp., Pythium spp., Piedraia hortai, Pneumocystis carinii, Puccinia spp., Pythium insidiosum, Rhinocladiella aquaspersa, Rhizomucor pusillus, Rhizoctonia spp., Rhizopus spp., Saccharomyces spp., Saksenaea vasiformis, Sarcinomycesphaeomuriformis, Scerotium spp., Sclerotinia spp., Sphaerotheca spp., Sporothrix schenckii, Syncephalastrum racemosum, Taeniolella boppii, Taphrina spp., Thielaviopsis spp., Toralopsosis spp., Trichophyton spp., Trichosporon spp., Ulocladium chartarum, Ustilago spp., Venturia spp., Verticillium spp., Wangiella dermatitidis, Whetxelinia spp., Xylohypha spp., and their synonyms.
122. The method of claim 121, wherein said fungal organism is selected from Candida spp.
123. The method of claim 111, wherein said supernatant is spent supernatant obtained from a source microorganism at the stationary phase.
124. The method of claim 111, wherein said supernatant is obtained from a source microorganism at the exponential phase.
125. The method of claim 124, wherein said source microorganism is at the early exponential phase.
126. The method of claim 124, wherein said source microorganism is at the mid exponential phase.
127. The method of claim 124, wherein said source microorganism is at the late exponential phase.
128. The method of claim 111, wherein said closed culture system comprises a source microorganism grown on a surface.
129. The method of claim 111, wherein said closed culture system comprises a source microorganism grown planktonically.
130. The method of claim 111, wherein said closed culture system comprises a source microorganism grown planktonically and on a surface.
131. The method of claim 111, wherein said supernatant has been treated to increase the concentration of a biofilm-modulating compound.
132. The method of claim 131, wherein said treatment comprises purification of said supernatant.
133. A method of potentiating the ability of an antimicrobial agent to decrease the viability of a microorganism within a biofilm, said method comprising exposing said microorganism to the supernatant of a closed culture system or an extract thereof.
134. The method of claim 133, wherein said biofilm comprises at least one target organism selected from the group consisting of achaea, bacteria, fungi, protozoa, and algae.
135. The method of claim 134, wherein said organism is a bacterial organism.
136. The method of claim 135, wherein said bacterial organism is selected from the group consisting of Pseudomonas fluorescens, Pseudomonas aeruginosa,
Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivalis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnet, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio paramaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, Bacteroides spp., Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actinomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp., Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Desulfosarcina spp., Deslfϊiromonas spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp., Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp., Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentificans, Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp.,
Chromobacterium spp., Saccharopolyspora spp., Actinobacillus spp., Alteromonas spp., Aeronomonas spp., Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus and Rhizobium spp., and mutant derivatives thereof.
137. The method of claim 136, wherein said bacterial organism is Pseudomonas aeruginosa.
138. The method of claim 136, wherein said bacterial organism is selected from Streptococcus spp.
139. The method of claim 136, wherein said bacterial organism is
Staphylococcus aureus.
140. The method of claim 136, wherein said bacterial organism is Staphylococcus epidermis.
141. The method of claim 135, wherein said bacterial organism is a coagulase-negative Staphylococcus.
142. The method of claim 134, wherein said target organism is a fungal organism.
143. The method of claim 142, wherein said fungal organism is selected from the group consisting of Absidia spp., Actinomadura madurae, Actinomyces spp., Allescheria boydii, Alternaria spp., Anthopsis deltoidea, Aphanomyces spp., Apophysomyces eleqans, Armillaria spp., Arniurn leoporinum, AspergiUus spp., Aureobasidium pullulans, Basidiobolus ranarum, Bipolaris spp., Blastomyces dermatitidis, Botrytis spp., Candida spp., Centrospora spp., Cephalosporium spp., Ceratocystis spp., Chaetoconidium spp., Chaetomium spp., Cladosporium spp., Coccidioides immitis, CoUetotrichum spp, Conidiobolus spp., Corynebacterium tenuis, Cryptoporiopsis spp., Cylindrocladium spp., Cryptococcus spp., Cunninghamella bertholletiae, Curvularia spp., Dactylaria spp., Diplodia spp., Epidermophyton spp., Epidermophyton floccosum, Exserophilum spp., Exophiala spp., Fonsecaea spp., Fulvia spp., Fusarium spp., Geotrichum spp., Guignardia spp., Helminthosporium spp., Histoplasma spp., Lecythophora spp., Macrophomina spp., Madurella spp., Magnaporthe spp., Malasseziafwfur, Microsporam spp., Monilinia spp., Mucor spp., Mycocentrospora acerina, Nectria spp., Nocardia spp., Oospora spp., Ophiobolus spp., Paecilomyces spp., Paracoccidioides brasiliensis, Penicillium spp., Phaeosclera dematioides, Phaeoannellomyces spp., Phialemonium obovatum, Phialophora spp., Phlyctaena spp., Phoma spp., Phomopsis spp., Phymatotrichum spp., Phytophthora spp., Pythium spp., Piedraia hortai, Pneumocystis carinii, Puccinia spp., Pythium insidiosum, Rhinocladiella aquaspersa, Rhizomucor pusillus, Rhizoctonia spp., Rhizopus spp., Saccharomyces spp., Saksenaea vasiformis, Sarcinomycesphaeomuriformis, Scerotium spp., Sclerotinia spp., Sphaerotheca spp., Sporofhrix schenckii, Syncephalastrum racemosum, Taeniolella boppii, Taphrina spp., Thielaviopsis spp., Toralopsosis spp., Trichophyton spp., Trichosporon spp., Ulocladium chartarum, Ustilago spp., Venturia spp., Verticillium spp., Wangiella dermatitidis, Whetxelinia spp., Xylohypha spp., and their synonyms.
144. The method of claim 143, wherein said fungal organism is selected from Candida spp.
145. The method of claim 134, wherein said supernatant is spent supernatant obtained from a source microorganism at the stationary phase.
146. The method of claim 134, wherein said supernatant is obtained from a source microorganism at the exponential phase.
147. The method of claim 146, wherein said source microorganism is at the early exponential phase.
148. The method of claim 146, wherein said source microorganism is at the mid exponential phase.
149. The method of claim 146, wherein said source microorganism is at the late exponential phase.
150. The method of claim 134, wherein said closed culture system comprises a source microorganism grown on a surface.
151. The method of claim 134, wherein said closed culture system comprises a source microorganism grown planktonically.
152. The method of claim 134, wherein said closed culture system comprises a source microorganism grown planktonically and on a surface.
153. The method of claim 134, wherein said supernatant has been treated to increase the concentration of a biofilm-modulating compound.
154. A method of modulating a biofilm-associated activity, said method comprising exposing said biofilm to the supernatant of a closed culture system or an extract thereof.
155. The method of claim 154, wherein said biofilm comprises at least one target organism selected from the group consisting of achaea, bacteria, fungi, protozoa, and algae.
156. The method of claim 155, wherein said organism is a bacterial organism.
157. The method of claim 156, wherein said bacterial organism is selected from the group consisting of Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivalis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio paramaernolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, Bacteroides spp., Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actinomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp., Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Desulfosarcina spp., Deslfuromonas spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp.,
Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp., Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentificans, Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp., Cliromobacterium spp., Saccharopolyspora spp., ActinobaciUus spp., Alteromonas spp., Aeronomonas spp., Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus and Rhizobium spp., and mutant derivatives thereof.
158. The method of claim 157, wherein said bacterial organism is Pseudomonas aeruginosa.
159. The method of claim 157, wherein said bacterial organism is selected from Streptococcus spp.
160. The method of claim 157, wherein said bacterial organism is Staphylococcus aureus.
161. The method of claim 157, wherein said bacterial organism is Staphylococcus epidermis.
162. The method of claim 156, wherein said bacterial organism is a coagulase-negative Staphylococcus.
163. The method of claim 155, wherein said target organism is a fungal organism.
164. The method of claim 163, wherein said fungal organism is selected from the group consisting of Absidia spp., Actinomadura madurae, Actinomyces spp., Allescheria boydii, Alternaria spp., Anthopsis deltoidea, Aphanomyces spp., Apophysomyces eleqans, Armillaria spp., Amium leoporinum, AspergiUus spp., Aureobasidium pullulans, Basidiobolus ranarum, Bipolaris spp., Blastomyces demiatitidis, Botrytis spp., Candida spp., Cenfrospora spp., Cephalosporium spp., Ceratocystis spp., Chaetoconidium spp., Chaetomium spp., Cladosporium spp., Coccidioides immitis, CoUetotrichum spp, Conidiobolus spp., Corynebacterium tenuis, Cryptoporiopsis spp., Cylindrocladium spp., Cryptococcus spp., Cunninghamella bertholletiae, Curvularia spp., Dactylaria spp., Diplodia spp., Epidermophyton spp., Epidermophyton floccosum, Exserophilum spp., Exophiala spp., Fonsecaea spp., Fulvia spp., Fusarium spp., Geotrichum spp., Guignardia spp., Helminthosporium spp., Histoplasma spp., Lecythophora spp., Macrophomina spp., Madurella spp., Magnaporthe spp., Malassezia furfur, Microsporam spp., Monilinia spp., Mucor spp., Mycocentrospora acerina, Nectria spp., Nocardia spp., Oospora spp., Ophiobolus spp., Paecilomyces spp., Paracoccidioides brasiliensis,
Penicillium spp., Phaeosclera dematioides, Phaeoannellomyces spp., Phialemonium obovatum, Phialophora spp., Phlyctaena spp., Phoma spp., Phomopsis spp., Phymatotrichum spp., Phytophthora spp., Pythium spp., Piedraia hortai, Pneumocystis carinii, Puccinia spp., Pythium insidiosum, Rhinocladiella aquaspersa, Rhizomucor pusillus, Rhizoctonia spp., Rhizopus spp., Saccharomyces spp., Saksenaea vasiformis, Sarcinomycesphaeomuriformis, Scerotium spp., Sclerotinia spp., Sphaerotheca spp., Sporothrix schenckii, Syncephalastrum racemosum, Taeniolella boppii, Taphrina spp., Thielaviopsis spp., Tomlopsosis spp., Trichophyton spp'., Trichosporon spp., Ulocladium chartarum, Ustilago spp., Venturia spp., Verticillium spp., Wangiella dermatitidis, Whetxelinia spp., Xylohypha spp., and their synonyms.
165. The method of claim 164, wherein said fungal organism is selected from Candida spp.
166. The method of claim 154, wherein said supernatant is spent supernatant obtained from a source microorganism at the stationary phase.
167. The method of claim 154, wherein said supernatant is obtained from a source microorganism at the exponential phase.
168. The method of claim 167, wherein said source microorganism is at the early exponential phase.
169. The method of claim 167, wherein said source microorganism is at the mid exponential phase.
170. The method of claim 167, wherein said source microorganism is at the late exponential phase.
171. The method of claim 154, wherein said closed culture system comprises a source microorganism grown on a surface.
172. The method of claim 154, wherein said closed culture system comprises a source microorganism grown planktonically.
173. The method of claim 154, wherein said closed culture system comprises a source microorganism grown planktonically and on a surface.
174. The method of claim 154, wherein said supernatant has been treated to increase the concentration of a biofilm-modulating compound.
175. The method of claim 174, wherein said treatment comprises purification of said supernatant.
176. The method of claim 89, wherein said formation is initial attachment of cells to a surface or development of the biofilm.
177. A compound comprising a chain of at least three rhamnose moieties linked to a lipid moiety and derivatives thereof.
178. The compound of claim 177, wherein said chain comprises seven rhamnose moieties.
179. The compound of claim 178, wherein said lipid moiety comprises a complex lipid containing an ester linkage.
180. A method for preventing a bacterium from participating in formation of a biofilm, said method comprising exposing said bacterium to a biological surfactant.
181. The method of claim 180, wherein said biological surfactant is a rhamnolipid compound.
182. The method of claim 181, wherein said rhamnolipid compound comprises a chain having at least three rhamnose moieties linked to a lipid moiety.
183. The method of claim 182, wherein said rhamnolipid compound comprises a chain of seven rhamnose moieties linked to a lipid moiety.
184. The method of claim 183, wherein said bacterium is selected from the group consisting of Pseudomonas fluorescens, Pseudomonas aeruginosa,
Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivalis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio paramaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, Bacteroides spp., Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actinomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp., Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Desulfosarcina spp., Deslfuromonas spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp., Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp., Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentificans, Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp.,
Chromobacterium spp., Saccharopolyspora spp., ActinobaciUus spp., Alteromonas spp., Aeronomonas spp., Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus and Rhizobium spp. , and mutant derivatives thereof.
185. The method of claim 184, wherein said bacterium is Pseudomonas aeruginosa.
186. The method of claim 184, wherein said bacterial organism is selected from Streptococcus spp.
187. The method of claim 184, wherein said bacterial organism is Staphylococcus aureus.
188. The method of claim 184, wherein said bacterial organism is Staphylococcus epidermis.
189. The method of claim 184, wherein said bacterial organism is a coagulase-negative Staphylococcus.
190. The method of claim 183, wherein said rhamnolipid compound is derived from supernatant of a closed culture system.
191. A biofilm modulating compound identified by the method comprising:
(a) obtaining supernatant from a closed culture system, said system comprising at least one type of a source microorganism; (b) exposing a target organism to said supernatant or an extract thereof; and
(c) measuring the level of said activity, wherein the compound is not an acyl homoserine lactone, a microbially- produced hydrolytic enzyme, a LactobociUus biosurfactant, or an autoinducing compound.
192. The compound of claim 191, wherein said compound is purified from supernatant from a closed culture system.
193. The compound of claim 191, wherein said compound is synthesized.
194. A method of modulating a biofilm, said method comprising exposing a target organism to the compound of claim 191.
195. The method of claim 194, wherein said modulating comprises inhibition of biofilm formation.
196. The method of claim 194, wherein said modulating comprises disruption of a preexisting biofilm.
197. The method of claim 194, wherein said modulating comprises promoting biofilm formation.
198. The method of claim 194, wherein said modulating comprises decreasing the viability of cells within said biofilm.
199. The method of claim 194, wherein said modulating comprises potentiating the ability of an antimicrobial agent to decrease the viability of cells within said biofilm.
200. The method of claim 194, wherein said biofilm comprises at least one target organism selected from the group consisting of archaea, bacteria, fungi, protozoa, and algae.
201. The method of claim 200, wherein said organism is a bacterial organism.
202. The method of claim 201 , wherein said bacterial organism is selected from the group consisting of Pseudomonas fluorescens, Pseudomonas aeruginosa,
Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivalis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabϊlis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio par amaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, Bacteroides spp., Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actinomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp., Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Desulfosarcina spp., Deslfuromonas spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp., Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp., Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentificans, Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp.,
Chromobacterium spp., Saccharopolyspora spp., ActinobaciUus spp., Alteromonas spp., Aeronomonas spp., Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus and Rhizobium spp. , and mutant derivatives thereof.
203. The method of claim 202, wherein said bacterial organism is Pseudomonas aeruginosa.
204. The method of claim 202, wherein said bacterial organism is selected from Streptococcus spp.
205. The method of claim 202, wherein said bacterial organism is
Staphylococcus aureus.
206. The method of claim 202, wherein said bacterial organism is Staphylococcus epidermis.
207. The method of claim 201 , wherein said bacterial organism is a coagulase-negative Staphylococcus .
208. The method of claim 200, wherein said target organism is a fungal organism.
209. The method of claim 208, wherein said fungal organism is selected from the group consisting of Absidia spp., Actinomadura madurae, Actinomyces spp., Allescheria boydii, Alternaria spp., Anthopsis deltoidea, Aphanomyces spp., Apophysomyces eleqans, Armillaria spp., A ium leoporinum, AspergiUus spp., Aureobasidium pullulans, Basidiobolus ranarum, Bipolaris spp., Blastomyces dermatitidis, Botrytis spp., Candida spp., Centrospora spp., Cephalosporium spp., Ceratocystis spp., Chaetoconidium spp., Chaetomium spp., Cladosporium spp., Coccidioides immitis, CoUetotrichum spp, Conidiobolus spp., Corynebacterium tenuis, Cryptoporiopsis spp., Cylindrocladium spp., Cryptococcus spp., Cunninghamella bertholletiae, Curvularia spp., Dactylaria spp., Diplodia spp., Epidermophyton spp., Epidermophyton floccosum, Exserophilum spp., Exophiala spp., Fonsecaea spp., Fulvia spp., Fusarium spp., Geotrichum spp., Guignardia spp., Helminthosporium spp., Histoplasma spp., Lecythophora spp., Macrophomina spp., Madurella spp., Magnaporthe spp., Malassezia furfur, Microsporam spp., Monilinia spp., Mucor spp., Mycocentrospora acerina, Nectria spp., Nocardia spp., Oospora spp., Ophiobolus spp., Paecilomyces spp., Paracoccidioides brasiliensis, Penicillium spp., Phaeosclera dematioides, Phaeoannellomyces spp., Phialemonium obovatum, Phialophora spp., Phlyctaena spp., Phoma spp., Phomopsis spp., Phymatotrichum spp., Phytophthora spp., Pythium spp., Piedraia hortai, Pneumocystis carinii, Puccinia spp., Pythium insidiosum, Rhinocladiella aquaspersa, Rhizomucor pusillus, Rhizoctonia spp., Rhizopus spp., Saccharomyces spp., Saksenaea vasiformis, Sarcinomycesphaeomuriformis, Scerotium spp., Sclerotinia spp., Sphaerotheca spp., Sporothrix schenckii, Syncephalastrum racemosum, Taeniolella boppii, Taphrina spp., Thielaviopsis spp., Tomlopsosis spp., Trichophyton spp., Trichosporon spp., Ulocladium chartarum, Ustilago spp., Venturia spp., Verticillium spp., Wangiella dermatitidis, Whetxelinia spp., Xylohypha spp., and their synonyms.
210. The method of claim 209, wherein said fungal organism is selected from Candida spp.
211. A method of potentiating the ability of an antimicrobial agent to decrease the viability of a microorganism within a biofilm, said method comprising exposing said microorganism to the supernatant of a closed culture system or an extract thereof.
212. The method of claim 211, wherein said biological surfactant is a rhamnolipid compound.
213. The method of claim 212, wherein said rhamnolipid compound comprises a chain having at least three rhamnose moieties linked to a lipid moiety.
214. The method of claim 213, wherein said rhamnolipid compound comprises a chain of seven rhamnose moieties linked to a lipid moiety.
215. The method of claim 214, wherein said microorganism is a bacterium selected from the group consisting of Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivdlis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica,
Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio paramaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis, Bacteroides spp., Clostridium difficile,
Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actinomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp., Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp., Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp., Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentificans, Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp., Chromobacterium spp., Saccharopolyspora spp., ActinobaciUus spp., Alteromonas spp., Aeronomonas spp., Desulfosarcina spp., Deslfuromonas spp., Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus and Rhizobium spp., and mutant derivatives thereof.
216. The method of claim 215, wherein said bacterium is Pseudomonas aeruginosa.
217. The method of claim 215, wherein said bacterial organism is selected from Streptococcus spp.
218. The method of claim 215, wherein said bacterial organism is Staphylococcus aureus.
219. The method of claim 215, wherein said bacterial organism is Staphylococcus epidermis.
220. The method of claim 215, wherein said bacterial organism is a coagulase-negative Staphylococcus.
221. The method of claim 211, wherein said rhamnolipid compound is derived from supernatant of a closed culture system.