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Published on: January 3, 2020
Database screening and in vivo efficacy of antimicrobial peptides against methicillin-resistant Staphylococcus aureus
Joseph Menousek1, Biswajit Mishra, Mark L Hanke
1Department of Microbiology and Pathology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198-6495, USA.
Abstract:
Natural antimicrobial peptides (AMPs) are promising candidates for developing a generation of new antimicrobials to meet the challenge of antibiotic-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). To facilitate the search for new candidates, we have utilised the Antimicrobial Peptide Database (APD), which contains natural AMPs from bacteria, fungi, plants and animals. This study demonstrates the identification of novel templates against MRSA by screening 30 peptides selected from the APD. These peptides are short (<25 residues), cysteine-free, cationic and represent candidates from different biological sources such as bacteria, insects, arachnids, tunicates, amphibians, fish and mammals. Six peptides, including ascaphin-8, database-screened antimicrobial peptide 1 (DASamP1), DASamP2, lycotoxin I, maculatin 1.3 and piscidin 1, were found to exert potent antimicrobial activity against an MRSA USA300 isolate. Although five of the six peptides showed broad-spectrum antibacterial activity, DASamP1 displayed killing of MRSA in vitro but not of Escherichia coli, Bacillus subtilis or Pseudomonas aeruginosa. In addition, DASamP1 suppressed early biofilm formation in a mouse model of catheter-associated MRSA infection. DASamP1 is a novel, short and potent peptide that will be a useful starting template for further developing novel anti-MRSA peptides.
Insights
Researchers screened natural antimicrobial peptides (AMPs) to combat antibiotic-resistant bacteria like MRSA. Six peptides showed potent activity, with DASamP1 effectively killing MRSA and inhibiting biofilm formation.
Area of Science:
- Biochemistry
- Microbiology
- Drug Discovery
Background:
- Antibiotic resistance, particularly from pathogens like methicillin-resistant Staphylococcus aureus (MRSA), necessitates novel antimicrobial agents.
- Natural antimicrobial peptides (AMPs) offer a promising avenue for developing new antimicrobials.
Purpose of the Study:
- To identify novel antimicrobial peptide templates effective against MRSA.
- To screen short, cysteine-free, cationic peptides from diverse biological sources.
Main Methods:
- Utilized the Antimicrobial Peptide Database (APD) to select 30 candidate peptides.
- Screened selected peptides for antimicrobial activity against an MRSA USA300 isolate.
- Evaluated the efficacy of promising peptides in a mouse model of catheter-associated MRSA infection.
Main Results:
- Six peptides (ascaphin-8, DASamP1, DASamP2, lycotoxin I, maculatin 1.3, piscidin 1) demonstrated potent activity against MRSA.
- DASamP1 exhibited specific killing of MRSA in vitro and suppressed early biofilm formation in vivo.
- Five peptides displayed broad-spectrum activity, while DASamP1 showed targeted MRSA efficacy.
Conclusions:
- DASamP1 is a novel, short, and potent antimicrobial peptide with significant potential for anti-MRSA drug development.
- The study identified promising peptide templates for combating antibiotic-resistant pathogens.
- Targeted screening of natural AMPs is an effective strategy for discovering new antimicrobial leads.
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