Protease Stabilized Antibacterial Peptides for S. aureus

Stephen Johnston (Inventor)

Research output: Patent

Abstract

Antimicrobial resistance (AMR) is a worldwide clinical and public health problem, primarily stemming from the overuse of antibiotics. One of the most critical resistant pathogens is Methicillin-resistant Staphylococcus aureus (MRSA) which has developed resistance to all beta-lactam antibiotics. Moreover, new antibiotics that are coming on the market are new derivatives of old antibiotics, so resistance will also likely develop to them. Natural antimicrobial peptides (AMPs) are well known as part of the innate immune system; however, despite being widely studied, issues with degradation and high manufacturing costs have limited the number of AMPs that have come to market. If useful forms of these antimicrobial peptides could be synthesized in the laboratory, they could prove an efficacious and low-cost therapeutic for treating drug-resistant bacterial infections. Researchers at the Biodesign Institute of Arizona State University have developed novel antimicrobial peptides, specific for Staphylococcus aureus. The first iteration of AMPs had dual-functionality; a targeting domain and a killing domain. The second generation of AMPs maintain their high activity levels but are also protease degradation resistant, which increases stability. In vivo testing of these peptides has shown no immunogenicity or acute toxicity at a 500 g dose, making them very attractive for antibiotic applications. Moreover, these peptides are less affected by the ever-increasing drug resistance of pathogens compared to conventional antibiotics. These antibiotic peptides, with their high specificity, protease stability, and lack of toxicity, provide a promising opportunity for a new generation of treatments for MRSA and MSSA. Potential Applications Treatment for Staphylococcus aureus infections Topical cream or suspension IP/IV-delivered drugs Peptide-polymer coatings for medical devices/implants Component of soaps/disinfectant liquids Benefits and Advantages Increased reactivity and specificity Broad spectra of action Protease stable 80% advantage in activity vs. separate components by themselves No immunogenicity or acute toxicity at 500 g dose Less apt to invoke drug resistance in bacteria Dowload Original PDF For more information about the inventor(s) and their research, please see Dr. Diehnelt's directory webpage Dr. Johnston's directory webpage
Original languageEnglish (US)
StatePublished - Apr 25 2014

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Peptide Hydrolases
Peptides
Anti-Bacterial Agents
Directories
Methicillin-Resistant Staphylococcus aureus
Drug Resistance
Staphylococcus aureus
Inventors
Costs and Cost Analysis
Soaps
Disinfectants
beta-Lactams
Microbial Drug Resistance
Bacterial Infections
Pharmaceutical Preparations
Immune System
Suspensions
Polymers
Therapeutics
Public Health

Cite this

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title = "Protease Stabilized Antibacterial Peptides for S. aureus",
abstract = "Antimicrobial resistance (AMR) is a worldwide clinical and public health problem, primarily stemming from the overuse of antibiotics. One of the most critical resistant pathogens is Methicillin-resistant Staphylococcus aureus (MRSA) which has developed resistance to all beta-lactam antibiotics. Moreover, new antibiotics that are coming on the market are new derivatives of old antibiotics, so resistance will also likely develop to them. Natural antimicrobial peptides (AMPs) are well known as part of the innate immune system; however, despite being widely studied, issues with degradation and high manufacturing costs have limited the number of AMPs that have come to market. If useful forms of these antimicrobial peptides could be synthesized in the laboratory, they could prove an efficacious and low-cost therapeutic for treating drug-resistant bacterial infections. Researchers at the Biodesign Institute of Arizona State University have developed novel antimicrobial peptides, specific for Staphylococcus aureus. The first iteration of AMPs had dual-functionality; a targeting domain and a killing domain. The second generation of AMPs maintain their high activity levels but are also protease degradation resistant, which increases stability. In vivo testing of these peptides has shown no immunogenicity or acute toxicity at a 500 g dose, making them very attractive for antibiotic applications. Moreover, these peptides are less affected by the ever-increasing drug resistance of pathogens compared to conventional antibiotics. These antibiotic peptides, with their high specificity, protease stability, and lack of toxicity, provide a promising opportunity for a new generation of treatments for MRSA and MSSA. Potential Applications Treatment for Staphylococcus aureus infections Topical cream or suspension IP/IV-delivered drugs Peptide-polymer coatings for medical devices/implants Component of soaps/disinfectant liquids Benefits and Advantages Increased reactivity and specificity Broad spectra of action Protease stable 80{\%} advantage in activity vs. separate components by themselves No immunogenicity or acute toxicity at 500 g dose Less apt to invoke drug resistance in bacteria Dowload Original PDF For more information about the inventor(s) and their research, please see Dr. Diehnelt's directory webpage Dr. Johnston's directory webpage",
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N2 - Antimicrobial resistance (AMR) is a worldwide clinical and public health problem, primarily stemming from the overuse of antibiotics. One of the most critical resistant pathogens is Methicillin-resistant Staphylococcus aureus (MRSA) which has developed resistance to all beta-lactam antibiotics. Moreover, new antibiotics that are coming on the market are new derivatives of old antibiotics, so resistance will also likely develop to them. Natural antimicrobial peptides (AMPs) are well known as part of the innate immune system; however, despite being widely studied, issues with degradation and high manufacturing costs have limited the number of AMPs that have come to market. If useful forms of these antimicrobial peptides could be synthesized in the laboratory, they could prove an efficacious and low-cost therapeutic for treating drug-resistant bacterial infections. Researchers at the Biodesign Institute of Arizona State University have developed novel antimicrobial peptides, specific for Staphylococcus aureus. The first iteration of AMPs had dual-functionality; a targeting domain and a killing domain. The second generation of AMPs maintain their high activity levels but are also protease degradation resistant, which increases stability. In vivo testing of these peptides has shown no immunogenicity or acute toxicity at a 500 g dose, making them very attractive for antibiotic applications. Moreover, these peptides are less affected by the ever-increasing drug resistance of pathogens compared to conventional antibiotics. These antibiotic peptides, with their high specificity, protease stability, and lack of toxicity, provide a promising opportunity for a new generation of treatments for MRSA and MSSA. Potential Applications Treatment for Staphylococcus aureus infections Topical cream or suspension IP/IV-delivered drugs Peptide-polymer coatings for medical devices/implants Component of soaps/disinfectant liquids Benefits and Advantages Increased reactivity and specificity Broad spectra of action Protease stable 80% advantage in activity vs. separate components by themselves No immunogenicity or acute toxicity at 500 g dose Less apt to invoke drug resistance in bacteria Dowload Original PDF For more information about the inventor(s) and their research, please see Dr. Diehnelt's directory webpage Dr. Johnston's directory webpage

AB - Antimicrobial resistance (AMR) is a worldwide clinical and public health problem, primarily stemming from the overuse of antibiotics. One of the most critical resistant pathogens is Methicillin-resistant Staphylococcus aureus (MRSA) which has developed resistance to all beta-lactam antibiotics. Moreover, new antibiotics that are coming on the market are new derivatives of old antibiotics, so resistance will also likely develop to them. Natural antimicrobial peptides (AMPs) are well known as part of the innate immune system; however, despite being widely studied, issues with degradation and high manufacturing costs have limited the number of AMPs that have come to market. If useful forms of these antimicrobial peptides could be synthesized in the laboratory, they could prove an efficacious and low-cost therapeutic for treating drug-resistant bacterial infections. Researchers at the Biodesign Institute of Arizona State University have developed novel antimicrobial peptides, specific for Staphylococcus aureus. The first iteration of AMPs had dual-functionality; a targeting domain and a killing domain. The second generation of AMPs maintain their high activity levels but are also protease degradation resistant, which increases stability. In vivo testing of these peptides has shown no immunogenicity or acute toxicity at a 500 g dose, making them very attractive for antibiotic applications. Moreover, these peptides are less affected by the ever-increasing drug resistance of pathogens compared to conventional antibiotics. These antibiotic peptides, with their high specificity, protease stability, and lack of toxicity, provide a promising opportunity for a new generation of treatments for MRSA and MSSA. Potential Applications Treatment for Staphylococcus aureus infections Topical cream or suspension IP/IV-delivered drugs Peptide-polymer coatings for medical devices/implants Component of soaps/disinfectant liquids Benefits and Advantages Increased reactivity and specificity Broad spectra of action Protease stable 80% advantage in activity vs. separate components by themselves No immunogenicity or acute toxicity at 500 g dose Less apt to invoke drug resistance in bacteria Dowload Original PDF For more information about the inventor(s) and their research, please see Dr. Diehnelt's directory webpage Dr. Johnston's directory webpage

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