Antimicrobial peptides and methods of using the same
Inventors
Jaynes, Jesse M. • Clemens, L. Edward • Lopez, Henry Wilfred • Martin, George R. • Woodburn, Kathryn
Assignees
Publication Number
US-11266712-B2
Publication Date
2022-03-08
Expiration Date
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Abstract
Aspects of the present invention relate to peptides having antimicrobial activity. In certain aspects, the invention relates to peptides having potent antimicrobial activity, broad-spectrum antimicrobial activity, and/or the ability to kill otherwise antibiotic-resistant microbes, or microbes protected by biofilms.
Core Innovation
The invention provides antimicrobial peptides and methods of using the same. The peptides of this disclosure can have anti-bacterial, anti-fungal, and/or anti-protozoal activity, and can kill microbial strains that are resistant to conventional antibiotics. This disclosure provides antimicrobial peptides that are capable of killing microbes (e.g., bacteria) growing as a microbial biofilm. The technology described and claimed below represents the first description of particular types of antimicrobial peptides that can be used a variety of applications, e.g., to selectively kill microbes (e.g., bacteria) for purposes of treatment of conditions related to microbial infections.
Antibiotic resistance is a major health problem and many emerging bacterial strains can exist in complex associations known as biofilms that are 20-1000 times more resistant to antibiotics than their planktonic counterparts. Broad-spectrum coverage for gram-negative pathogens and multidrug-resistant gram-positive bacteria is limited and frequent outbreaks occur, and there is an urgent need for materials that are active against antibiotic resistant organisms in both free and biofilm form. Acute bacterial skin and skin structure infections (ABSSSI) are responsible for substantial hospitalizations and cost, and biofilms can form on chronic wounds and medical implants where they have the potential to cause systemic infections.
The antimicrobial peptides generally include an amphipathic or striapathic region, and in some cases include two amphipathic or striapathic regions separated by a linking region or bubble region. As described, amphipathic regions can adopt amphipathic secondary structures and can have a cationic surface, and peptides of the disclosure can include tail regions, bubble regions, β-turn regions, and can form dimers to enhance antimicrobial activity. The disclosure provides specific peptide sequences (e.g., RP550-RP567 and variants) and describes compositions and methods for administering such antimicrobial peptides to a subject to prevent or treat a microbial infection.
Claims Coverage
One independent claim was identified (claim 1) and it recites three main alternative peptide definitions.
Peptide sequence selection
a peptide sequence selected from RP550-557 (SEQ ID NO: 1 to SEQ ID NO: 8), RP559-562 (SEQ ID NO: 10 to SEQ ID NO: 13), RP566 (SEQ ID NO: 17) or RP567 (SEQ ID NO: 18)
Sequence identity alternative
a sequence having at least 90% sequence identity with the sequence defined in a)
Limited conservative substitutions alternative
a sequence having three or less amino acid substitutions relative to the sequence defined in a), wherein the three or less amino acid substitutions are conservative amino acid substitutions according to Table 3
Claim 1 covers peptides defined by selection of specific RP sequences, sequences with high sequence identity to those sequences, and sequences with up to three conservative amino acid substitutions as defined in Table 3.
Stated Advantages
Peptides having potent antimicrobial activity.
Peptides having broad-spectrum antimicrobial activity.
Ability to kill microbial strains that are resistant to conventional antibiotics.
Capability to kill microbes growing as a microbial biofilm.
Reduced risk of development of pathogen resistance as evidenced by statements that bacteria did not develop resistance to exemplary peptides.
Use to selectively kill microbes for purposes of treatment of conditions related to microbial infections.
Documented Applications
Treating or preventing microbial infections caused by bacteria, viruses, fungi, and parasites by administering a therapeutically effective amount of a subject peptide to a subject in need thereof.
Inhibiting or eradicating biofilms and treating biofilm-associated infections, including biofilms on chronic wounds and medical implants.
Topical treatment of infected wounds and burns, including demonstration of dose-dependent reduction of bacterial burden in an infected porcine burn model [procedural detail omitted for safety].
Ophthalmic application for treatment of eye diseases or conditions, including topical instillation (eye drops), subconjunctival, intravitreal, retrobulbar, or intracameral administration, and use in ophthalmic formulations.
Coating or incorporating peptides on the surface of medical devices or implantable devices to prevent infection and biofilm formation on indwelling devices and implants.
Inhalation administration for pulmonary delivery, including aerosolized formulations and liposome-encapsulated peptide delivery to the lungs.
Treatment of vaginal candidiasis via topical administration, with efficacy demonstrated in a rodent vaginal infection model [procedural detail omitted for safety].
Use as an antimicrobial preservative, disinfectant, or sterile storage medium for devices such as contact lenses, intraocular lens implants, or drug-eluting ocular devices.
Combination use with additional bioactive agents including conventional antibiotics, anti-inflammatory drugs, anti-nausea drugs, and anti-pain medications as part of pharmaceutical compositions.
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