Antimicrobial peptides and methods of use thereof
Inventors
Jaynes, Jesse • Clemens, L. Edward • Lopez, Henry W. • Martin, George R. • Woodburn, Kathryn
Assignees
Publication Number
US-10017542-B2
Publication Date
2018-07-10
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
Antibiotic resistance is a major health problem attributed in part to the widespread use of antibiotics in medicine, agriculture and animal husbandry, which has created a selection bias toward antibiotic resistant bacteria. In addition to exhibiting inherited antibiotic resistance, many emerging bacterial strains can exist in complex associations known as biofilm, and the structure of the biofilm constitutes a physical barrier to antibiotic exposure. Biofilms can form in and on tissues, particularly on chronic wounds and medical implants, where they have the potential to cause systemic infections. There is an urgent need for materials that are active against antibiotic resistant organisms in both free and biofilm form.
The invention provides antimicrobial peptides having antimicrobial activity, including peptides having potent antimicrobial activity, broad-spectrum antimicrobial activity, and the ability to kill microbial strains that are resistant to conventional antibiotics and microbes growing as a microbial biofilm. In certain embodiments, antimicrobial peptides of the invention have amphipathic structure coupled with an overall cationic charge, hydrophobicity, volume, and mass that generates affinity for specific microbial membrane regions and include at least one amphipathic region. The antimicrobial peptides can include two amphipathic regions linked together by a third region, such as a bubble region or a beta-turn, and the two amphipathic regions can dimerize as a heterodimer or homodimer. The invention further provides compositions, including pharmaceutical compositions, and methods of treating or prophylactically preventing microbial infections by administering compositions containing one or more antimicrobial peptides of the invention, and coating medical devices with antimicrobial peptides.
Claims Coverage
This section identifies 4 independent claims and extracts their main inventive features.
Antimicrobial composition comprising an antimicrobial peptide
wherein the antimicrobial peptide comprises an amino acid sequence having at least 90% sequence identity to one of SEQ ID NOs: 3, 5, 8, 18, 22, 23 and 25-30.
Antimicrobial composition comprising an antimicrobial peptide (SEQ ID NO: 21)
wherein the antimicrobial peptide comprises the amino acid sequence of SEQ ID NO: 21.
Antimicrobial composition comprising an antimicrobial peptide (SEQ ID NOs: 6 and 20)
wherein the antimicrobial peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 6 and 20.
Antimicrobial composition comprising an antimicrobial peptide (SEQ ID NO: 19)
wherein the antimicrobial peptide comprises the amino acid sequence of SEQ ID NO: 19.
The independent claims recite antimicrobial compositions defined by peptides having specified SEQ ID NO sequences or high sequence identity to listed SEQ ID NOs, and include standalone compositions directed to peptides of SEQ ID NOs: 21, 6, 20, and 19.
Stated Advantages
Potent antimicrobial activity.
Broad-spectrum antimicrobial activity.
Ability to kill otherwise antibiotic-resistant microbes.
Ability to kill microbes growing as a microbial biofilm.
Specificity for non-mammalian cells, e.g., peptides can be 102, 103, 104, 105 times, or more effective at killing target microbial cells as compared to killing host mammalian cells.
Hairpin or beta-turn linked dimer structures can significantly enhance antimicrobial activity and polyproline helix structures can result in extended half-life.
Documented Applications
Treating microbial infections or prophylactically preventing such infections by administering a composition containing one or more antimicrobial peptides of the invention.
Administration routes including oral, parenteral, and topical delivery, and formulating pharmaceutical compositions for these routes.
Topical administration to treat wounds or burns and topical delivery as a gel, cream, microneedle, infusion into a bandage or topical patch to extend duration of action.
Formulating oral compositions with an enteric coat to ensure peptides reach the intestine and beyond.
Coating the surface of medical devices, such as surgical instruments and indwelling medical devices (e.g., pacemakers, catheters, artificial joints), to prevent infection.
Use in pharmaceutical compositions that include a pharmaceutically acceptable carrier and optionally additional bioactive agents such as conventional antibiotics or other therapeutic agents.
Treating a wide range of animals including humans, domesticated animals, farm animals, zoo animals, and wild animals.
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