The antibacterial activity of LI-F type peptide against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and inhibition of infections in murine scalded epidermis
LI-F type peptides are a family of cyclic lipodepsipeptide antibiotics isolated from Paenibacillus polymyxa and display potent activities against positive bacteria including methicillin-resistant S. aureus (MRSA). In this study, we investigated the mechanism of action of LI-F type peptide AMP-jsa9 against a MRSA (S. aureus CICC10790), which is resistant to ciprofloxacin, gentamicin, kanamycin, chloramphenicol, methicillin, and tetracycline. It was found that AMP-jsa9 mainly targets the cell membrane of MRSA and is able to inhibit biofilm formation through killing planktonic bacteria cells. Moreover, AMP-jsa9 can bind to DNA in vitro, which represents another pathway for the action on MRSA. Furthermore, in vivo treatment of scalded mice with AMP-jsa9 resulted in inhibiting MRSA infections and healing of the scalded wound. In addition, it was demonstrated that AMP-jsa9 can effectively inhibit MRSA infections in scalded murine epidermis and that inflammatory cytokines including IL-8, IL-6, tumor necrosis factor alpha (TNF-α), and monocyte chemotactic factor-1 (MCP-1) were reduced; moreover, both protein and gene expression levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (e-NOS) were enhanced, which promote neovascularization and proliferation of new granulation tissue.
KeywordsMRSA Infection AMP-jsa9 Antimicrobial activity Scalded mice Treatment
Compliance with ethical standards
All procedures performed in studies involving animals were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with humans performed by any of the authors.
Conflict of interest
The authors declare that they have no conflict of interest.
- Babavalian H, Latifi AM, Shokrgozar MA, Bonakdar S, Mohammadi S, Moghaddam MM (2015) Analysis of healing effect of alginate sulfate hydrogel dressing containing antimicrobial peptide on wound infection caused by methicillin-resistant Staphylococcus aureus. Jundishapur J Microbiol 8(9)Google Scholar
- Barawkar DA, Bruice TC (1998) Synthesis, biophysical properties, and nuclease resistance properties of mixed backbone oligodeoxynucleotides containing cationic internucleoside guanidinium linkages: deoxynucleic guanidine/DNA chimeras. Proc Natl Acad Sci U S A 95(19):11047–11052. https://doi.org/10.1073/pnas.95.19.11047 CrossRefPubMedPubMedCentralGoogle Scholar
- Cázaresdomínguez V, Cruzcórdova A, Ochoa SA, Escalona G, Arellanogalindo J, Rodríguezleviz A, Hernándezcastro R, Lópezvillegas EO, Xicohtencatlcortes J (2015) Vancomycin tolerant, methicillin-resistant Staphylococcus aureus reveals the effects of vancomycin on cell wall thickening. PLoS One 10(3)Google Scholar
- Ferrara N (1996) Vascular endothelial growth factor. Arterioscl Thromb Vasc 32A(14):2413Google Scholar
- Haisma EM, De BA, Chan H, van Dissel JT, Drijfhout JW, Hiemstra PS, El GA, Nibbering PH (2014) LL-37-derived peptides eradicate multidrug-resistant Staphylococcus aureus from thermally wounded human skin equivalents. Antimicrob Agents Chemother 58(8):4411–4419. https://doi.org/10.1128/AAC.02554-14 CrossRefPubMedPubMedCentralGoogle Scholar
- Hu J, Zhang X, Liu X, Chen C, Sun B (2015) Mechanism of reduced vancomycin susceptibility conferred by walK mutation in community-acquired methicillin-resistant Staphylococcus aureus strain MW2. Antimicrob Agents Chemother 59(2):1352–1355. https://doi.org/10.1128/AAC.04290-14 CrossRefPubMedPubMedCentralGoogle Scholar
- Huang HN, Rajanbabu V, Pan CY, Chan YL, Wu CJ, Chen JY (2013) Use of the antimicrobial peptide Epinecidin-1 to protect against MRSA infection in mice with skin injuries. Biomaterials 34(38):10319–10327. https://doi.org/10.1016/j.biomaterials.2013.09.037 CrossRefPubMedGoogle Scholar
- Kearns RD, Cairns CB, Iv JHH (2013) Cairns BA burn injury: what’s in a name? Labels used for burn injury classification—a review of the data 2000–2012 poster. In: Southern Burn ConferenceGoogle Scholar
- Sun Y, Dong W, Sun L, Ma L, Shang D (2015) Insights into the membrane interaction mechanism and antibacterial properties of chensinin-1b. Biomaterials 37:299–311. https://doi.org/10.1016/j.biomaterials.2014.10.041 CrossRefPubMedGoogle Scholar
- Zhou H, Dou J, Wang J, Chen L, Wang H, Zhou W, Li Y, Zhou C (2011) The antibacterial activity of BF-30 in vitro and in infected burned rats is through interference with cytoplasmic membrane integrity. Peptides 32(6):1131–1138. https://doi.org/10.1016/j.peptides.2011.04.002 CrossRefPubMedGoogle Scholar