Applied Microbiology and Biotechnology

, Volume 102, Issue 5, pp 2301–2311 | Cite as

The antibacterial activity of LI-F type peptide against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and inhibition of infections in murine scalded epidermis

  • Jinzhi Han
  • Zhi Ma
  • Peng Gao
  • Zhaoxin Lu
  • Hongxia Liu
  • Ling Gao
  • Wenjun Lu
  • Xiangyu Ju
  • Fengxia Lv
  • Haizhen Zhao
  • Xiaomei Bie
Applied microbial and cell physiology

Abstract

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.

Keywords

MRSA Infection AMP-jsa9 Antimicrobial activity Scalded mice Treatment 

Notes

Compliance with ethical standards

Ethical statement

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.

Supplementary material

253_2017_8669_MOESM1_ESM.pdf (1.3 mb)
ESM 1 (PDF 1379 kb).

References

  1. Alekshun MN, Levy SB (2007) Molecular mechanisms of antibacterial multidrug resistance. Cell 128(6):1037–1050.  https://doi.org/10.1016/j.cell.2007.03.004 CrossRefPubMedGoogle Scholar
  2. Alonso-Sarduy L, Roduit C, Dietler G, Kasas S (2011) Human topoisomerase II–DNA interaction study by using atomic force microscopy. FEBS Lett 585(19):3139–3145.  https://doi.org/10.1016/j.febslet.2011.08.051 CrossRefPubMedGoogle Scholar
  3. 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
  4. 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
  5. Bionda N, Stawikowski M, Stawikowska R, Cudic M, López-Vallejo F, Treitl D, Medina-Franco J, Cudic P (2012) Effects of cyclic lipodepsipeptide structural modulation on stability, antibacterial activity, and human cell toxicity. Chem Med Chem 7(5):871–882CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bionda N, Pitteloud J-P, Cudic P (2013) Cyclic lipodepsipeptides: a new class of antibacterial agents in the battle against resistant bacteria. Future Med Chem 5(11):1311–1330.  https://doi.org/10.4155/fmc.13.86 CrossRefPubMedGoogle Scholar
  7. Boylevavra S, Carey RB, Daum RS (2001) Development of vancomycin and lysostaphin resistance in a methicillin-resistant Staphylococcus aureus isolate. J Antimicrob Chemother 48(48):617–625.  https://doi.org/10.1093/jac/48.5.617 CrossRefGoogle Scholar
  8. Browne KA, Dempcy RO, Bruice TC (1995) Binding studies of cationic thymidyl deoxyribonucleic guanidine to RNA homopolynucleotides. Proc Natl Acad Sci U S A 92(15):7051–7055.  https://doi.org/10.1073/pnas.92.15.7051 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 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
  10. Demidova TN, Gad F, Zahra T, Francis KP, Hamblin MR (2005) Monitoring photodynamic therapy of localized infections by bioluminescence imaging of genetically engineered bacteria. J Photoch Photobio O B 81(1):15–25.  https://doi.org/10.1016/j.jphotobiol.2005.05.007 CrossRefGoogle Scholar
  11. Deng Y, Lu Z, Bi H, Lu F, Zhang C, Bie X (2011a) Isolation and characterization of peptide antibiotics LI-F04 and polymyxin B produced by Paenibacillus polymyxa strain JSa-9. Peptides 32(9):1917–1923.  https://doi.org/10.1016/j.peptides.2011.08.004 CrossRefPubMedGoogle Scholar
  12. Deng Y, Lu Z, Lu F, Zhang C, Wang Y, Zhao H, Bie X (2011b) Identification of LI-F type antibiotics and di-n-butyl phthalate produced by Paenibacillus polymyxa. J Microbiol Methods 85:175–182CrossRefPubMedGoogle Scholar
  13. Ferrara N (1996) Vascular endothelial growth factor. Arterioscl Thromb Vasc 32A(14):2413Google Scholar
  14. Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18(1):4–25CrossRefPubMedGoogle Scholar
  15. Gemmell CG, Edwards DI, Fraise AP, Gould FK, Ridgway GL, Warren RE (2006) Guidelines for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the UK. J Antimicrob Chemother 57(4):589–608.  https://doi.org/10.1093/jac/dkl017 CrossRefPubMedGoogle Scholar
  16. Gould IM (2006) Costs of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) and its control. Int J Antimicrob Agents 28(5):379–384.  https://doi.org/10.1016/j.ijantimicag.2006.09.001 CrossRefPubMedGoogle Scholar
  17. 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
  18. Han J, Gao P, Zhao S, Bie X, Lu Z, Zhang C, Lv F (2017a) iTRAQ-based proteomic analysis of LI-F type peptides produced by Paenibacillus polymyxa JSa-9 mode of action against Bacillus cereus. J Proteome 150:130–140.  https://doi.org/10.1016/j.jprot.2016.08.019 CrossRefGoogle Scholar
  19. Han J, Zhao S, Ma Z, Gao L, Liu H, Muhammad U, Lu Z, Lv F, Bie X (2017b) The antibacterial activity and modes of LI-F type antimicrobial peptides against Bacillus cereus in vitro. J Appl Microbiol 123(3):602–614.  https://doi.org/10.1111/jam.13526 CrossRefPubMedGoogle Scholar
  20. Hartman BJ, Tomasz A (1984) Low-affinity penicillin-binding protein associated with beta-lactam resistance in Staphylococcus aureus. J Bacteriol 158(2):513–516PubMedPubMedCentralGoogle Scholar
  21. Hiramatsu K (2001) Vancomycin-resistant Staphylococcus aureus : a new model of antibiotic resistance. Lancet Infect Dis 1(3):147–155.  https://doi.org/10.1016/S1473-3099(01)00091-3 CrossRefPubMedGoogle Scholar
  22. 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
  23. 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
  24. 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
  25. Mccarthy H, Rudkin JK, Black NS, Gallagher L, O’Neill E, O'Gara JP (2015) Methicillin resistance and the biofilm phenotype in Staphylococcus aureus. Front Cell Infect Microbiol 5(1):1PubMedPubMedCentralGoogle Scholar
  26. Ong ZY, Gao SJ, Yang YY (2013) Short synthetic β-sheet forming peptide Amphiphiles as broad spectrum antimicrobials with antibiofilm and endotoxin neutralizing capabilities. Adv Funct Mater 23(29):3682–3692.  https://doi.org/10.1002/adfm.201202850 CrossRefGoogle Scholar
  27. Sharma SK, Dai T, Kharkwal GB, Huang YY, Huang L, Arce VJBD, Tegos GP, Hamblin RM (2011) Drug discovery of antimicrobial photosensitizers using animal models. Curr Pharm Des 17(13):1303–1319.  https://doi.org/10.2174/138161211795703735 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Stallmeyer B, Anhold M, Wetzler C, Kahlina K, Pfeilschifter J, Frank S (2002) Regulation of eNOS in normal and diabetes-impaired skin repair: implications for tissue regeneration. Nitric Oxide Biol Chem 6(2):168–177.  https://doi.org/10.1006/niox.2001.0407 CrossRefGoogle Scholar
  29. 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
  30. Tai CC, Nirvani AA, Holmes A, Hughes SP (2004) Methicillin-resistant Staphylococcus aureus in orthopaedic surgery. Int Orthop 28(1):32–35.  https://doi.org/10.1007/s00264-003-0505-2 CrossRefPubMedGoogle Scholar
  31. Utsui Y, Yokota T (1985) Role of an altered penicillin-binding protein in methicillin-and cephem-resistant Staphylococcus aureus. Antimicrob Agents Chemother 28(3):397–403.  https://doi.org/10.1128/AAC.28.3.397 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Walsh C (2000) Molecular mechanisms that confer antibacterial drug resistance. Nature 406(6797):775–781.  https://doi.org/10.1038/35021219 CrossRefPubMedGoogle Scholar
  33. Witte MB, Barbul A (2002) Role of nitric oxide in wound repair. Am J Surg 183(4):406–412.  https://doi.org/10.1016/S0002-9610(02)00815-2 CrossRefPubMedGoogle Scholar
  34. 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

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jinzhi Han
    • 1
  • Zhi Ma
    • 1
  • Peng Gao
    • 1
  • Zhaoxin Lu
    • 1
  • Hongxia Liu
    • 1
  • Ling Gao
    • 1
  • Wenjun Lu
    • 1
  • Xiangyu Ju
    • 1
  • Fengxia Lv
    • 1
  • Haizhen Zhao
    • 1
  • Xiaomei Bie
    • 1
  1. 1.College of Food Science and Technology, Key Laboratory of Food Processing and Quality Control, Ministry of Agriculture of ChinaNanjing Agricultural UniversityNanjingPeople’s Republic of China

Personalised recommendations