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Publication Number
US-10273272-B2
Publication Date
2019-04-30
Expiration Date
Abstract
The present invention provides novel antimicrobial peptides and nucleic acids encoding them, the peptides having an inhibitory or bactericidal/bacteriostatic effect on both Gram-negative and Gram-positive bacteria. The invention includes methods of treating bacterial infections and preventing the spread of the infections or contamination by the infection. The peptides of the present invention are of particular use as therapeutics to treat Gram-negative infections and are of use in impregnation, covering or coating medical devices or implants or prosthetics prior to introduction into a patient's body.
Core Innovation
The invention relates to isolated or recombinant antimicrobial peptides derived from epidermicin (Staphylococcus epidermidis). The disclosure provides specific peptide sequences selected from SFEWIYKQIFKLWA [SEQ ID NO:1], SFEWIKYQIKKLWA [SEQ ID NO:2], SFEWIYKQIWKLKRGLA [SEQ ID NO:3], formyl-SFKWIYKQIKKLWA [SEQ ID NO:4], SFKWIYKQIKKLWA [SEQ ID NO:5], SFEWIYKQIKKLWAK [SEQ ID NO:6], and SFEWIYKQIKKLWAKKK [SEQ ID NO:7]. Nucleic acids encoding these peptides are also described.
The invention addresses bacterial infections by providing peptide variants that exhibit bactericidal and bacteriostatic activity against both Gram-positive bacteria and Gram-negative bacteria. The disclosure emphasizes antimicrobial activity including Gram-negative potency and includes inhibition of biofilm formation. The document also discusses designer-antibiotic tailoring by sequence modification of epidermicin variants and associated structural modeling, including secondary/3D predictions.
The invention further provides uses of the antimicrobial peptides for treating or preventing bacterial infection spread and for incorporation into medical and dental contexts. The peptides are described for coating, impregnating, or otherwise providing peptide-containing medical devices and implants, as well as dental preparations.
Claims Coverage
Two independent claim types are presented: peptide claims and nucleic acid claims. The coverage is grounded on defined sequence membership for seven peptide sequences and corresponding nucleic acids encoding those sequences.
Isolated or recombinant peptide comprising selected antimicrobial sequences
An isolated or recombinant peptide comprising a sequence selected from the group consisting of SFEWIYKQIFKLWA [SEQ ID NO:1], SFEWIKYQIKKLWA [SEQ ID NO:2], SFEWIYKQIWKLKRGLA [SEQ ID NO:3], formyl-SFKWIYKQIKKLWA [SEQ ID NO:4], SFKWIYKQIKKLWA [SEQ ID NO:5], SFEWIYKQIKKLWAK [SEQ ID NO:6], and SFEWIYKQIKKLWAKKK [SEQ ID NO:7].
Isolated or recombinant nucleic acid encoding selected antimicrobial sequences
An isolated or recombinant nucleic acid sequence comprising a sequence encoding a peptide comprising a sequence selected from the group consisting of SFEWIYKQIFKLWA [SEQ ID NO:1], SFEWIKYQIKKLWA [SEQ ID NO:2], SFEWIYKQIWKLKRGLA [SEQ ID NO:3], formyl-SFKWIYKQIKKLWA [SEQ ID NO:4], SFKWIYKQIKKLWA [SEQ ID NO:5], SFEWIYKQIKKLWAK [SEQ ID NO:6], and SFEWIYKQIKKLWAKKK [SEQ ID NO:7].
The main inventive coverage centers on peptide variants defined by exact sequence set membership, including a formylated variant and sequence variants with additional residues, together with corresponding nucleic acids encoding those peptides.
Stated Advantages
Bactericidal and bacteriostatic activity against both Gram-positive bacteria and Gram-negative bacteria.
Inhibition of biofilm formation.
Therapeutic potential supported by haemolysis/toxicity results described in the disclosure.
Documented Applications
Treating or preventing bacterial infection spread using the antimicrobial peptides.
Coating, impregnating, or providing peptide-containing medical devices and implants.
Dental preparations comprising one or more of the peptides, including spray, mouthwash, gel, paste, lozenge, and chewing gum.
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