Compounds and methods for biofilm disruption and prevention

1. A pharmaceutical or anti-biofouling composition for disrupting a biofilm or preventing biofilm formation comprising an isolated microbial deoxyribonuclease polypeptide and an excipient, wherein said composition is coated on at least a portion of a patient-contactable surface of an indwelling medical device, and wherein the microbial deoxyribonuclease is as set forth in SEQ ID NO. 4.

2. The composition of claim 1 further comprising an antimicrobial compound.

3. The composition of claim 2 wherein the antimicrobial compound is an antiparasitic compound which is one or more of a benzazole; a macrocycle; pyrantel pamoate; diethylcarbamazine; niclosamide; praziquantel; melarsoprol; and eflornithine.

4. The composition of claim 2 wherein the antimicrobial compound is an antiviral compound which is one or more of a nucleoside analog reverse transcriptase inhibitor; an uncoating inhibitor; a protease inhibitor; zanamivir; oseltamivir; and rifampin.

5. The composition of claim 2 wherein the antimicrobial compound is an antibacterial compound which is one or more of an aminoglycoside; a beta-lactam; a cephalosporin; a quinolone; a macrolide; an oxazolidinone; an ansamycin; a sulphonamide; a tetracycline; a glycopeptide; sulfisoxazole, trimethoprim, novobiocin, daptomycin and linezolid.

6. The composition of claim 2 wherein the antimicrobial compound is an antifungal compound which is one or more of an azole, a macrocycle, an allyl amine, an echinocandin, polygodial, ciclopyrox, tolnaftate, benzoic acid, undecylenic acid, flucytosine and griseofulvin.

7. The composition of claim 2 wherein the composition is an anti-biofouling composition and the antimicrobial compound is an antibacterial compound which is a parahydroxy benzoic acid ester (parabens).

8. A method of preventing or disrupting a biofilm on a surface comprising contacting the surface with an effective dose of the composition of claim 1 , wherein the surface is at least a portion of a patient-contactable surface of an indwelling medical device.

9. The method of claim 8 wherein said surface is a surface of a catheter.

10. The method of claim 8 wherein the microbial deoxyribonuclease of said composition is attached to said surface.

11. The composition of claim 1 wherein said device is a catheter.

12. A method of preventing or disrupting a biofilm on a surface comprising:

expressing a microbial deoxyribonuclease polypeptide from an expression vector that comprises a polynucleotide encoding the microbial deoxyribonuclease; and

contacting the surface with an effective dose of the microbial deoxyribonuclease polypeptide, wherein the surface is at least a portion of a patient-contactable surface of an indwelling medical device, wherein the microbial deoxyribonuclease is as set forth in SEQ ID NO: 4.

13. The composition of claim 1 wherein said composition is attached to said at least a portion of the patient-contactable surface of said device.

14. The composition of claim 2 wherein said antimicrobial compound is an antibacterial compound, an antiparasitic compound, an antifungal compound or an antiviral compound.

15. The composition of claim 3 wherein:

said benzazole is albendazole, mebendazole or tiabendazole; or

said azole is metronidazole or tinidazole; or

said macrocycle is amphotericin B, rifampin or ivermectin.

16. The composition of claim 4 wherein:

said nucleoside analog reverse transcriptase inhibitor is acyclovir, didanosine, stavudine, zidovudine, lamivudine, abacavir, emtricitabine or entecavir; or

said uncoating inhibitor is amantadine, rimantadine or pleconaril; or

said protease inhibitor is saquinavir, ritonavir, indinavir, nelfinavir or amprenavir.

17. The composition of claim 5 wherein:

said aminoglycoside is gentamicin, kanamycin or streptomycin; or

said beta-lactam is penicillin, ampicillin or imipenem; or

said cephalosporin is ceftazidime, or

said quinolone is ciprofloxacin; or

said macrolide is azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin or telithromycin; or

said oxazolidinone is linezolid; or

said ansamycin is rifamycin; or

said tetracycline is doxycycline; or

said glycopeptide is vancomycin.

18. The composition of claim 6 wherein:

said azole is miconazole, ketoconazole, clotrimazole, econazole, omoconazole, bifonazole, butoconazole, fenticonazole, isoconazole, sertaconazole, sulconazole, tioconazole, fluconazole, itraconazole, isavuconazole, ravuconazole, posaconazole, voriconazole, terconazole or abafungin; or

said macrocycle is natamycin, rimocidin, filipin, nystatin, amphotericin B, candicin or hamycin; or

said allyl amine is terbinafine, naftifine or butenafine; or

said echinocandin is andidulafungin, caspofungin or micafungin.

19. The composition of claim 7 wherein said parahydroxy benzoic acid ester is methyl-paraben, ethyl-paraben, propyl-paraben, butyl-paraben or benzyl-paraben.

20. The method of claim 8 wherein said surface is a surface of a central venous catheter, intravascular catheter, urinary catheter, Hickman catheter, peritoneal dialysis catheter, endrotracheal catheter, or the surface of a mechanical heart valve, a cardiac pacemaker, an arteriovenous shunt, a schleral buckle, a prosthetic joint, a tympanostomy tube, a tracheostomy tube, a voice prosthetic, a penile prosthetic, an artificial urinary sphincter, a synthetic pubovaginal sling, a surgical suture, a bone anchor, a bone screw, an intraocular lens, a contact lens, an intrauterine device, an aortofemoral graft, a vascular graft, a needle, a Luer-Lok connector, a needleless connector or a surgical instrument.

21. The composition of claim 1 wherein said device is a central venous catheter, intravascular catheter, urinary catheter, Hickman catheter, peritoneal dialysis catheter, endrotracheal catheter, or wherein the device is a mechanical heart valve, a cardiac pacemaker, an arteriovenous shunt, a schleral buckle, a prosthetic joint, a tympanostomy tube, a tracheostomy tube, a voice prosthetic, a penile prosthetic, an artificial urinary sphincter, a synthetic pubovaginal sling, a surgical suture, a bone anchor, a bone screw, an intraocular lens, a contact lens, an intrauterine device, an aortofemoral graft, a vascular graft, a needle, a Luer-Lok connector, a needleless connector or a surgical instrument.