Compositions and methods for the removal of biofilms
AssigneesUniversity of Southern California, Nationwide Children's Hospital, Inc.
InventorsSTEVEN D. GOODMAN, LAUREN O. BAKALETZ
Life of this patent
Estimating the term…
Abstract
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.
Claims48
A method for inhibiting, competing or titrating the binding of a DNABII polypeptide or protein to a microbial DNA, comprising contacting the DNABII polypeptide or protein or the microbial DNA with an interfering agent, thereby inhibiting, competing or titrating the binding of the DNABII protein or polypeptide to the microbial DNA.
A method for inhibiting, preventing or breaking down a microbial biofilm, comprising contacting the biofilm with an interfering agent, thereby inhibiting, preventing or breaking down the microbial biofilm.
A method of inhibiting, preventing or breaking down a biofilm in a subject, comprising administering to the subject an effective amount of an interfering agent, thereby inhibiting, preventing or breaking down the microbial biofilm.
A method for inhibiting, preventing or treating a microbial infection that produces a biofilm in a subject, comprising administering to the subject an effective amount of an interfering agent, thereby inhibiting, preventing or treating a microbial infection that produces the biofilm in the subject.
A method for inducing an immune response in or conferring passive immunity on a subject in need thereof, comprising administering to the subject an effective amount of one or more agents of the group:
- (a) an isolated or recombinant integration host factor (IHF) polypeptide, or a fragment or an equivalent of each thereof;
- (b) an isolated or recombinant histone-like protein from E. coli strain U93 (HU) polypeptide or a fragment or an equivalent of each thereof;
- (c) an isolated or recombinant protein polypeptide identified in Table 8, Table 9A, Table 9B, Table 10 or a DNA binding peptide identified in FIG. 6, or a fragment or an equivalent of each thereof;
- (d) an isolated or recombinant polypeptide SEQ ID NO. 1 through 340, or a fragment or an equivalent of each thereof;
- (e) an isolated or recombinant C-terminal polypeptide of SEQ ID NO. 6 through 11, 28, 29, 42 through 100, Table 8 or those C-terminal polypeptides identified in Table 10, or a fragment or equivalent of each thereof;
- (f) an isolated or recombinant polynucleotide encoding any one polypeptide of (a) through (e) or an isolated or recombinant polynucleotide of SEQ ID NO. 36 or an equivalent of each thereof, or a polynucleotide that hybridizes under stringent conditions to the polynucleotide, its equivalent or its complement;
- (g) an antibody or antigen binding fragment that specifically recognizes or binds any one of (a) through (e), or an equivalent or fragment of each thereof;
- (h) an isolated or recombinant polynucleotide encoding the antibody or antigen binding fragment of (g);
- (i) an antigen presenting cell pulsed with any one of (a) through (e);
- or
- (i) an antigen presenting cell transfected with one or more polynucleotides encoding any one of (a) through (e).
An isolated or recombinant polypeptide consisting essentially of an amino acid sequence selected from SEQ ID NO. 1 to 5;
- 12 to 27;
- 30-35;
- 101-340 or a DNA binding peptide identified in FIG. 6, or an equivalent of each thereof.
An isolated or recombinant polypeptide comprising two or more of any of SEQ ID NO. 1 to 5;
- 12 to 27;
- 30-35;
- 101-340;
- a DNA binding peptide identified in FIG. 6, or an equivalent of each thereof, with the proviso that the polypeptide is none of SEQ ID NOS. 6 to 11, 28, 29 or 42-100.
A method of identifying an agent that modulates the binding of a DNABII protein or polypeptide to a microbial DNA in a sample containing the same, comprising contacting a candidate agent with the sample, and assaying for the binding of the protein or polypeptide to the DNA, wherein the agent modulates the binding by inhibiting, preventing or titrating the binding of the DNABII protein or polypeptide to the microbial DNA.
A method for identifying a patient having a microbial infection that is likely or is not likely to be treated by the administration of an interfering agent, comprising detecting the presence or absence of a DNABII polypeptide or protein in sample isolated from the patient and containing the infection, wherein the presence of the DNABII polypeptide or protein identifies the patient as likely to be treated by the administration of the interfering agent and the absence of a DNABII polypeptide or protein identifies the patient as not likely to be treated by the administration of the interfering agent.
A computer-implemented method for identifying an agent that inhibits, competes or titrates the binding of a DNABII polypeptide or protein to a microbial DNA, that inhibits, prevents or breaks down a microbial biofilm, that inhibits, prevents or breaks down a biofilm in a subject, or that inhibits, prevents or treats a microbial infection that produces a biofilm in a subject, comprising positioning a three-dimensional structure of a candidate agent against a three-dimensional structure of an integration host factor (IHF) protein, wherein the three-dimensional structure of the IHF protein is based on X, Y and Z atomic structure coordinates determined from a crystalline form of an IHF and DNA complex, wherein interaction of the agent with the IHF at two or more IHF amino acids selected from T4, K5, A6, E28, Q43, K45, S47, G48, N51, R55, K57, R60, R63, N64, P65, K66, R76, T80, R82 or Q85 as represented in SEQ ID NO:
- 42, or the equivalent of each, identifies that the agent inhibits, competes or titrates the binding of a DNABII polypeptide or protein to a microbial DNA, inhibits, prevents or breaks down a microbial biofilm, inhibits, prevents or breaks down a biofilm, or inhibits, prevents or treats a microbial infection that produces a biofilm.
A custom computing apparatus comprising:
- at least one processor;
- a memory coupled to the at least one processor;
- a storage medium in communication with the memory and the at least one processor, the storage medium containing a set of processor executable instructions that, when executed by the processor configure the custom computing apparatus to identify an agent that inhibits, competes or titrates the binding of a DNABII polypeptide or protein to a microbial DNA, that inhibits, prevents or breaks down a microbial biofilm, that inhibits, prevents or breaks down a biofilm in a subject, or that inhibits, prevents or treats a microbial infection that produces a biofilm in a subject, wherein the configuration comprises:
- positioning a three-dimensional structure of a candidate agent against a three-dimensional structure of an integration host factor Win protein, wherein the three-dimensional structure of the IHF protein is based on Y and Z atomic structure coordinates determined from a crystalline form of an IHF and DNA complex, wherein interaction of the agent with the IHF at two or more IHF amino acids selected from T4, K5, A6, E28, Q43, K45, S47, G48, N51, R55, K57, R60, R63, N64, P65, K66, R76, T80, R82 or Q85 as represented in SEQ ID NO:
- 42, or the equivalent of each, identifies that the agent inhibits, competes or titrates the binding of a DNABII polypeptide or protein to a microbial DNA, inhibits, prevents or breaks down a microbial biofilm, inhibits, prevents or breaks down a biofilm, or inhibits, prevents or treats a microbial infection that produces a biofilm.
Dependencies are inferred from the claim text.