Compositions and methods for the removal of biofilms

摘要

This invention provides isolated or recombinant polypeptides that are useful to vaccinate individuals suffering from chronic/recurrent biofilm disease or as a therapeutic for those with an existing infection. The individual's immune system will then naturally generate antibodies which prevent or clear these bacteria from the host by interfering with the construction and or maintenance of a functional protective biofilm. Alternatively, antibodies to the polypeptides can be administered to treat or prevent infection. Bacteria that cannot form functional biofilms are more readily cleared by the remainder of the host's immune system.

主权项

1. A method for inhibiting, preventing or breaking down a microbial biofilm in a subject, comprising administering to the subject an effective amount of an interfering agent, wherein the interfering agent is selected from the group of:
(a) an isolated or recombinant integration host factor (IHF) polypeptide or an immunogenic fragment or an equivalent of each thereof wherein the fragment or equivalent thereof inhibits, prevents or breaks down a microbial biofilm; (b) an isolated or recombinant histone-like protein from E. coli strain U93 (HU) polypeptide or an immunogenic fragment or an equivalent of each thereof wherein the fragment or equivalent thereof inhibits, prevents or breaks down a microbial biofilm; (c) an isolated or recombinant protein or polypeptide selected from the group of 1310 (HU), Spy1239 (HU), SGO—0701 (HIpA), SAG—0505 (Hup), Smu—589 (HU), spr1020 (HU), YP—003430069 (HIpA), MW1362 (HU), SERP1041 (Hup), b1712 (HimA), b0912 (HimD), (HupA), (HupB), HI1221 (HimA), HI1313 (HimD), HI0430 (HupA), Sty1771 (HimA), Sty0982 (HimD), YP—003255965 (IHFalpha), YP—003256209 (IhfB), YP—003255304 (HU), FG—0121 (Hup-1), PG—1258 (Hup-2), NGO603 (IHFβ), NGO030 α), NMB—0729 (HimA), NMB—1302 (HimA), PA3161 (HimD), PA1804 (HupB), PA2758 (HimA), Hp0835 (Hup), BB—0232 (Hbb), YP—003626307 (HimA), YP—003627027 (HimD), YP—003626775 (HupB), VC—0273 (HupA), VC—1914 (HipB), VC—1919 (HupB), VC—1222 (HimA), Bcen2424—1048 (IHFB), Bcen2424—1481 (IHFA), BURPS668—2881 (IHFB), BURPS668—1718 (IHFA), MT—3064 (HU), MSMEG—2389 (Hup), TDE—1709 (HU), TP—0251 (DNA binding protein II), PREME0022—2103 (HupB), PREME0022—0268 (HupA), PREME0022—0341 (Hup), PREME0022—0340 (HimA), PIN_A0704 (Hup), PIN_A1504 (Hup-2), PIN—0345 (HimA), PIN—0343 (Hypothetical protein), BP2572 (IhfA), BP3530 (HupB), BP0951 (IhfB), Ef1550 (hup), (SEQ ID NOS: 42-76), (SEQ ID NOS: 101-128), (SEQ ID NOS:16-336) or a DNA binding peptide identified in (SEQ ID NOS: 1-36 and 337-340), or a fragment or an equivalent of each thereof wherein the fragment or equivalent thereof inhibits, prevents or breaks down a microbial biofilm; (d) an isolated or recombinant polypeptide of SEQ ID NO. 1 through 340, or an equivalent of each thereof, or a fragment or an equivalent of each fragment thereof wherein the fragment or equivalent thereof inhibits, prevents or breaks down a microbial biofilm; (e) an isolated or recombinant C-terminal polypeptide of SEQ ID NO. 6 through 11, 28, 29, 42 through 100, an isolated or recombinant protein or polypeptide selected from the group of 1310 (HU), Spy1239 (HU), SGO—0701 (HIpA), SAG—0505 (Hup), Smu—589 (HU), spr1020 (HU), YP—003430069 (HIpA), MW1362 (HU), SERP1041 (Hup), b1712 (HimA), b0912 (HimD), (HupA), (HupB), HI1221 (HimA), HI1313 (HimD), HI0430 (HupA), Sty1771 (HimA), Sty0982 (HimD), YP—003255965 (IHFalpha), YP—003256209 (IhfB), YP—003255304 (HU), FG—0121 (Hup-1), PG—1258 (Hup-2), NGO603 (IHFβ), NGO030 α), NMB—0729 (HimA), NMB—1302 (HimA), PA3161 (HimD), PA1804 (HupB), PA2758 (HimA), Hp0835 (Hup), BB—0232 (Hbb), YP—003626307 (HimA), YP—003627027 (HimD), YP—003626775 (HupB), VC—0273 (HupA), VC—1914 (HipB), VC—1919 (HupB), VC—1222 (HimA), Bcen2424—1048 (IHFB), Bcen2424—1481 (IHFA), BURPS668—2881 (IHFB), BURPS668—1718 (IHFA), MT—3064 (HU), MSMEG—2389 (Hup), TDE—1709 (HU), TP—0251 (DNA binding protein II), PREME0022—2103 (HupB), PREME0022—0268 (HupA), PREME0022—0341 (Hup), PREME0022—0340 (HimA), PIN_A0704 (Hup), PIN_A1504 (Hup-2), PIN—0345 (HimA), PIN—0343 (Hypothetical protein), BP2572 (IhfA), BP3530 (HupB), BP0951 (IhfB), Ef1550 (hup) or SEQ IDS NOS: 160-336 or a fragment or an equivalent of each thereof wherein the fragment or equivalent thereof inhibits, prevents or breaks down a microbial biofilm; (f) a polypeptide or polynucleotide that competes with an integration host factor on binding to a microbial DNA; (g) a four-way junction polynucleotide resembling a Holliday junction, a 3 way junction poly-nucleotide resembling a replication fork, a polynucleotide that has inherent flexibility or bent polynucleotide; (h) an isolated or recombinant polynucleotide encoding any one of (a) through (t) or an isolated or recombinant polynucleotide of SEQ ID NO. 36 or an immunogenic equivalent of each thereof, or a polynucleotide that hybridizes under stringent conditions to the polynucleotide or its complement wherein the fragment or equivalent thereof inhibits, prevents or breaks down a microbial biofilm; (i) an antibody or antigen binding fragment that specifically recognizes or binds any one of (a) through (f), or an equivalent or fragment of each antibody or antigen binding fragment thereof wherein the fragment or equivalent thereof inhibits, prevents or breaks down a microbial biofilm; (j) an isolated or recombinant polynucleotide encoding the antibody or antigen binding fragment of (i) or its complement; (k) a small molecule that competes with the binding of a DNABII protein or polypeptide to a microbial DNA; or (l) an isolated or recombinant DNABII polypeptide or a fragment or an equivalent of each thereof wherein the fragment or equivalent thereof inhibits, prevents or breaks down a microbial biofilm.