title: Activity of tick antimicrobial peptide from Ixodes persulcatus (persulcatusin) against cell membranes of drug-resistant Staphylococcus aureus.
abstract: Persulcatusin (IP), which is an antimicrobial peptide found in Ixodes persulcatus midgut, is active against Gram-positive bacteria such as Staphylococcus aureus. Multidrug-resistant bacteria in particular methicillin-resistant S. aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA) are a worldwide clinical concern. In the present study, to explore the potential of IP as a new agent against multidrug-resistant S. aureus infections, we evaluated the antimicrobial activity of IP against multidrug-resistant S. aureus strains by MIC90, morphological observation with scanning electron microscope (SEM), and the calcein leakage assay of membrane integrity. Among the six antimicrobial peptides used in this study, IP exhibited the lowest MIC90values for both vancomycin-susceptible and -resistant S. aureus strains. The IP MIC90against a VISA strain was equivalent to vancomycin, while the MIC90against VRSA was relatively low. SEM observations indicated that bacterial cells exposed to IP were crumpled and showed prominent structural changes. Moreover, IP influenced the cell membranes of both MRSA and VRSA in a mere 5 min, leading to leakage of the preloaded calcein. Although a VISA strain was resistant to the action of IP on cell membrane, the MIC90of IP was lower than that of Nisin, suggesting that IP had another bactericidal mechanism in addition to cell membrane attack. Our results indicate that the synthetic tick antimicrobial peptide, IP exhibits strong antibacterial activity against multidrug-resistant S. aureus strains, including VRSA, via both cell membrane attack and another unknown mechanism. IP represents a promising candidate for a new anti-VRSA therapy.
authors.affiliation: Department of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Miyagi, Japan.
authors.forename: Naruhide
authors.initials: N
authors.lastname: Miyoshi
authors.affiliation: Department of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Miyagi, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Isogai
authors.affiliation: Department of Microbiology, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramatsu
authors.affiliation: Department of Microbiology, Faculty of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects*; D024901:Drug Resistance, Multiple, Bacterial; D018884:Ixodes / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C000618144:persulcatusin