Dispersion and detachment of cell aggregates

Inventors

Zlotkin, Amir

Assignees

Dispersebio Ltd

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Publication Number

US-9700058-B2

Patent

Publication Date

2017-07-11

Expiration Date


Abstract

Compositions comprising a protein or isolated peptide, and methods using the same for preventing, dispersing or detaching a biofilm, are disclosed.

Core Innovation

The invention is directed to anti-biofilm/anti-adhesive compositions based on specific protein/peptide sequences, including cyclic and linker-conjugated variants, that detach single-cell organisms or biofilm aggregates from surfaces and/or each other. The compositions are also described as reducing exopolysaccharide matrix formation associated with biofilms.

The document further characterizes cyclic peptides defined by an amino-acid sequence pattern (SEQ ID NO: 1) with variable positions X1–X12 constrained to specified allowed residues, together with a cyclization linker between X1 and X12, and a total peptide length of up to 50 amino acids. Example cyclic peptides and variants are identified by named sequences and enumerated peptide sequences, including a cyclic peptide that is not SVPYDYNWYSNW (SEQ ID NO: 2).

From the described background and experimental summaries, the problem addressed is microbial adhesion and biofilm formation, including the formation of an exopolysaccharide matrix, which contributes to persistent infection and attachment-related pathology. The compositions are described as dispersing and detaching biofilms and as preventing adhesion across multiple microbes, with reported reductions in Congo Red/Trypan Blue binding and enhanced antibiotic and antifungal effectiveness in combination with antibacterial and/or antifungal agents.

Claims Coverage

The document provides three independent claim groupings, one peptide structural claim and two application or utility-related claim groupings. Across these independent claims, the inventive features focus on a cyclic peptide defined by constrained amino-acid positions plus cyclization linker constraints, compositions containing the peptide, and methods that contact organisms or treat biofilm-bearing environments to detach or disperse biofilms, optionally in combination with specific antibacterial and antifungal agents.

Cyclic peptide with constrained sequence positions and exclusion

A peptide consisting of amino acids X1-X12 (SEQ ID NO: 1), wherein X1–X12 are restricted to specified sets of allowed residues, wherein the peptide is cyclic, and wherein the peptide is not SVPYDYNWYSNW (SEQ ID NO: 2).

Cyclic peptide with cyclization linker between X1 and X12

A cyclic peptide consisting of an amino acid sequence X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 (SEQ ID NO: 1) with X1–X12 restricted to specified allowed residues, and a cyclization linker between X1 and X12, wherein the cyclic peptide has a total length of up to 50 amino acids.

Detaching a single cell organism by contacting with cyclic peptide

A method of detaching a single cell organism from a surface or from other single cell organisms, comprising contacting said organism with a cyclic peptide consisting of SEQ ID NO: 1 constrained X1–X12 residues, a cyclization linker between X1 and X12, and wherein the cyclic peptide has a total length of up to 50 amino acids.

Overall, claim coverage is anchored by cyclic peptides defined using SEQ ID NO: 1 and residue-position constraints, cyclization linker features, and a length limit of up to 50 amino acids, with the utility anchored to contacting a single cell organism to detach it from a surface or other organisms.

Stated Advantages

Detaches single-cell organisms or biofilm aggregates from surfaces and/or each other.

Reduces exopolysaccharide matrix formation and biofilm persistence through dispersal and detachment.

Prevents adhesion across multiple microbes.

Enhances antibacterial and/or antifungal effectiveness when used in combination with antibacterial and/or antifungal agents.

Reduces Congo Red/Trypan Blue binding as reported in the document.

Documented Applications

Prevention and/or treatment of pathogen infections involving biofilms, including in vivo biofilms.

Detaching or dispersing biofilms in water or detaching biofilm formation from a surface by treating water and/or coating a surface with an anti-adhesive or anti-biofilm composition.

Coating medical devices and surfaces to prevent biofouling and device-related infections.

Using the anti-biofilm composition in combination with antibacterial and/or antifungal agents to enhance activity.

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