Aili WANG,Yan CHEN,Haining YU,et al.Novel Cathelicidins with Potent Antimicrobial, Biofilm Inhibitory, and Anti-inflammatory Activities from the Frog Fejervarya multistriata[J].Asian Herpetological Reserch(AHR),2017,8(3):199-212.[doi:10.16373/j.cnki.ahr.160067]
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Novel Cathelicidins with Potent Antimicrobial, Biofilm Inhibitory, and Anti-inflammatory Activities from the Frog Fejervarya multistriata
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Asian Herpetological Research[ISSN:2095-0357/CN:51-1735/Q]

2017 VoI.8 No.3
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Novel Cathelicidins with Potent Antimicrobial, Biofilm Inhibitory, and Anti-inflammatory Activities from the Frog Fejervarya multistriata
Aili WANG1 Yan CHEN2 Haining YU3* Yipeng WANG2*
1 Weifang University of Science and Technology, Shouguang 262700, Shandong, China
2 Department of Pharmaceutical Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu, China
3 Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian 116023, Liaoning, China
cathelicidin Fejervarya multistriata FM-CATHs antimicrobial peptide bacterial biofilm anti-inflammatory
Antimicrobial peptides (AMPs),?a class of gene-encoded peptides, are the first line of immune system to defense microbial invasions in multicellular organisms. Cathelicidins are an important family of AMPs that have been identified exclusively in vertebrates. However, up to now, cathelicidins from amphibians are poorly understood. In the present study, we reported the identification and characterization of two novel cathelicidins (FM-CATH1 and FM-CATH2) from the frog Fejervarya multistriata. The cDNA sequences encoding FM-CATHs were successfully cloned from the constructed lung cDNA library of F. multistriata. Both of the cDNA sequences encoding FM-CATHs are 447 bp in length, and the deduced mature peptides of FM-CATHs are composed of 34 residues. Structural analysis indicated that FM-CATH1 and FM-CATH2 mainly assume amphipathic alpha-helical conformations. Antimicrobial and bacterial killing kinetic analysis indicated that both FM-CATH1 and FM-CATH2 possess potent, broad-spectrum and rapid antimicrobial potency. And cytoplasmic membrane permeabilization analysis indicated that FM-CATH1 and FM-CATH2 kill bacteria by inducing the permeabilization of bacterial membrane. Besides direct antimicrobial activities, FM-CATHs also exhibited significant inhibitory effect on the formation of bacterial biofilms at low concentrations below 1×MIC. Furthermore, FM-CATH1 and FM-CATH2 exhibited potent anti-inflammatory activities by inhibiting LPS-induced transcription and production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in mouse peritoneal macrophages. Meanwhile, FM-CATHs showed relatively low cytotoxic activity against mammalian normal and tumor cell lines, and low hemolytic activity against human erythrocytes. In summary, the identification of FM-CATHs provides novel clues for our understanding of the roles of cathelicidins in amphibian immune systems. The potent antimicrobial, biofilm inhibitory, anti-inflammatory activities, and low cytotoxicity of FM-CATHs imply their great potential in novel antibiotics development.


Akira S., Uematsu S., Takeuchi O. 2006. Pathogen recognition and innate immunity. Cell, 124: 783–801
Brogden K. A. 2005. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol, 3: 238–250
Brown K. L., Poon G. F., Birkenhead D., Pena O. M., Falsafi R., Dahlgren C., Karlsson A., Bylund J., Hancock R. E., Johnson P. 2011. Host defense peptide LL-37 selectively reduces proinflammatory macrophage responses. J Immunol, 186: 5497–5505
Davies D. 2003. Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov, 2: 114–122
De Zoysa G. H., Cameron A. J., Hegde V. V., Raghothama S., Sarojini V. 2015. Antimicrobial peptides with potential for biofilm eradication: synthesis and structure activity relationship studies of battacin peptides. J Med Chem, 58: 625–639
Elad S., Epstein J. B., Raber-Durlacher J., Donnelly P., Strahilevitz J. 2012. The antimicrobial effect of Iseganan HCl oral solution in patients receiving stomatotoxic chemotherapy: analysis from a multicenter, double-blind, placebo-controlled, randomized, phase III clinical trial. J Oral Pathol Med, 41: 229–234
Gennaro R., Skerlavaj B., Romeo D. 1989. Purification, composition, and activity of two bactenecins, antibacterial peptides of bovine neutrophils. Infect Immun, 57: 3142–3146
Hall-Stoodley L., Costerton J. W., Stoodley P. 2004. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol, 2: 95–108
Hancock R. E., Nijnik A., Philpott D. J. 2012. Modulating immunity as a therapy for bacterial infections. Nat Rev Microbiol, 10: 243–254
Hancock R. E., Sahl H. G. 2006. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol, 24: 1551–1557
Hao X., Yang H. L., Wei L., Yang S. L., Zhu W. J., Ma D. Y., Yu H. N., Lai R. 2012. Amphibian cathelicidin fills the evolutionary gap of cathelicidin in vertebrate. Amino Acids, 43: 677–685
Isaacson R. E. 2003. MBI-226. Micrologix/Fujisawa. Curr Opin Investig Drugs, 4: 999–1003
Janssens J. C., Steenackers H., Robijns S., Gellens E., Levin J., Zhao H., Hermans K., De Coster D., Verhoeven T. L., Marchal K., Vanderleyden J., De Vos D. E., De Keersmaecker S. C. 2008. Brominated furanones inhibit biofilm formation by Salmonella enterica serovar Typhimurium. Appl Environ Microbiol, 74: 6639–6648
Ling G. Y., Gao J. X., Zhang S. M., Xie Z. P., Wei L., Yu H. N., Wang Y. P. 2012. Cathelicidins from the bullfrog Rana catesbeiana provides novel template for peptide antibiotic design. PLoS One, 9: e93216
Mookherjee N., Brown K. L., Bowdish D. M., Doria S., Falsafi R., Hokamp K., Roche F. M., Mu R., Doho G. H., Pistolic J., Powers J. P., Bryan J., Brinkman F. S., Hancock R. E. 2006. Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J Immunol, 176: 2455–2464
Nakatsuji T., Gallo R.L. 2012. Antimicrobial peptides: old molecules with new ideas. J Invest Dermatol, 132: 887–895
Nguyen L. T., Haney E. F., Vogel H. J. 2011. The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol, 29: 464–472
Radek K., Gallo R. 2007. Antimicrobial peptides: natural effectors of the innate immune system. Semin Immunopathol, 29: 27–43
Rawlinson L. A., Ryan S. M., Mantovani G., Syrett J. A., Haddleton D. M., Brayden D. J. 2010. Antibacterial effects of poly(2-(dimethylamino ethyl)methacrylate) against selected gram-positive and gram-negative bacteria. Biomacromolecules, 11: 443–453
Scott M. G., Davidson D. J., Gold M. R., Bowdish D., Hancock R. E. 2002. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol, 169: 3883–3891
Scott M. G., Dullaghan E., Mookherjee N., Glavas N., Waldbrook M., Thompson A., Thompson A., Wang A., Lee K., Doria S., Hamill P., Yu J. J., Li Y., Donini O., Guarna M. M., Finlay B. B., North J. R., Hancock R. E. 2007. An anti-infective peptide that selectively modulates the innate immune response. Nat Biotechnol, 25: 465–472
Steiner H., Hultmark D., Engstrom A., Bennich H., Boman H. G. 1981. Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature, 292: 246–248
Steinstraesser L., Kraneburg U., Jacobsen F., Al-Benna S. 2011. Host defense peptides and their antimicrobial-immunomodulatory duality. Immunobiology, 216: 322–333
Tosi M. F. 2005. Innate immune responses to infection. J Allergy Clin Immunol, 116: 241–249; quiz 250
Wang Y. P., Zhang Z. Y., Chen L. L., Guang H. J., Li Z., Yang H. L., Li J. X., You D. W., Yu H. N., Lai R. 2011. Cathelicidin-BF, a snake cathelicidin-derived antimicrobial peptide, could be an excellent therapeutic agent for acne vulgaris. PLoS One, 6: e22120
Wei L., Gao J. X., Zhang S. M., Wu S. J., Xie Z. P., Ling G. Y., Kuang Y. Q., Yang Y. L., Yu H. N., Wang Y. P. 2015. Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism. J Biol Chem, 290: 16633–16652
Wei L., Yang J. J., He X. Q., Mo G. X., Hong J., Yan X. W., Lin D. H., Lai R. 2012. Structure and function of a potent lipopolysaccharide-binding antimicrobial and anti-inflammatory peptide. J Med Chem, 56: 3546–3556
Wong J. H., Ye X. J., Ng T. B. 2013. Cathelicidins: peptides with antimicrobial, immunomodulatory, anti-inflammatory, angiogenic, anticancer and procancer activities. Curr Protein Pept Sci, 14: 504–514
Xiao Y., Cai Y., Bommineni Y. R., Fernando S. C., Prakash O., Gilliland S. E., Zhang G. 2006. Identification and functional characterization of three chicken cathelicidins with potent antimicrobial activity. J Biol Chem, 281: 2858–2867
Yu H. N., Cai S. S., Gao J. X., Zhang S. Y., Lu Y. L., Qiao X., Yang H. L., Wang Y. P. 2013. Identification and polymorphism discovery of the cathelicidins, Lf-CATHs in ranid amphibian (Limnonectes fragilis). FEBS J, 280: 6022–6032
Zanetti M. 2004. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol, 75: 39–48
Zanetti M., Gennaro R., Scocchi M., Skerlavaj B. 2000. Structure and biology of cathelicidins. Adv Exp Med Biol, 479: 203–218
Zanetti M., Litteri L., Gennaro R., Horstmann H., Romeo D. 1990. Bactenecins, defense polypeptides of bovine neutrophils, are generated from precursor molecules stored in the large granules. J Cell Biol, 111: 1363–1371
Zasloff M. 2002. Antimicrobial peptides of multicellular organisms. Nature, 415: 389–395


Last Update: 2017-09-25