title: Database screening and in vivo efficacy of antimicrobial peptides against methicillin-resistant Staphylococcus aureus USA300.
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.
authors.affiliation: Department of Microbiology and Pathology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198-6495, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Menousek
authors.forename: Biswajit
authors.initials: B
authors.lastname: Mishra
authors.forename: Mark L
authors.initials: ML
authors.lastname: Hanke
authors.forename: Cortney E
authors.initials: CE
authors.lastname: Heim
authors.forename: Tammy
authors.initials: T
authors.lastname: Kielian
authors.forename: Guangshun
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D001412:Bacillus subtilis / Q000187:drug effects; D001426:Bacterial Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000187:drug effects; D005656:Fungal Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D010940:Plant Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D005656:Fungal Proteins; D010940:Plant Proteins