Abstract
Recently, the mortality of life-threatening fungal infections increased dramatically. However, there are few antifungals existed. Antimicrobial peptides (AMPs) as promising antifungal candidates have attracted much attention. Here, we present a small antimicrobial peptide Jelleine-I that had potent in vitro and in vivo antifungal activity. Negligible hemolytic activity and in vivo toxicity were observed. Selectivity index (SI) of Jelleine-I is at least 4.6 times higher than amphotericin B. Jelleine-I could increase the production of cellular ROS and bind with genome DNA. This may contribute to its antifungal activity. Furthermore, drug resistance is not induced when the fungal cells were repeatedly treated by Jelleine-I. In conclusion, our results suggest that Jelleine-I may have the potential to be developed as a novel antifungal agent.
Similar content being viewed by others
References
Asthana N, Yadav SP, Ghosh JK (2004) Dissection of antibacterial and toxic activity of melittin: a leucine zipper motif plays a crucial role in determining its hemolytic activity but not antibacterial activity. J Biol Chem 279(53):55042–55050
Berman J, Sudbery PE (2002) Candida albicans: a molecular revolution built on lessons from budding yeast. Nat Rev Genet 3(12):918–930
Boman HG, Dan H (1987) Cell-free immunity in insects. Annu Rev Microbiol 41(41):103–126
Cabrera MPDS, Baldissera G, Silva-Gonçalves LDC, Souza BMD, Riske KA, Palma MS, Ruggiero JR, Arcisio-Miranda M (2014) Combining experimental evidence and molecular dynamic simulations to understand the mechanism of action of the antimicrobial octapeptide Jelleine-I. Biochemistry 53(29):4857–4868
Chen C, Cooper SL (2002) Interactions between dendrimer biocides and bacterial membranes. Biomaterials 23(16):3359–3368
Chen Y, Mant CT, Farmer SW, Hancock RE, Vasil ML, Hodges RS (2005) Rational design of alpha-helical antimicrobial peptides with enhanced activities and specificity/therapeutic index. J Biol Chem 280(13):12316–12329
Chen Y, Zhang S, Li B, Qiu W, Jiao B, Zhang J, Diao Z (2008) Expression of a cytotoxic cationic antibacterial peptide in Escherichia coli using two fusion partners. Protein Expr Purif 57(2):303–311
Chou H, Kuo T, Chiang J, Pei M, Yang W, Yu H, Lin S, Chen WJ (2008) Design and synthesis of cationic antimicrobial peptides with improved activity and selectivity against Vibrio spp. Int J Antimicrob Agents 32(2):130–138
Cuenca-Estrella M, Gomez-Lopez A, Alastruey-Izquierdo A, Bernal-Martinez L, Cuesta I, Buitrago MJ, Rodriguez-Tudela JL (2010) Comparison of the Vitek 2 antifungal susceptibility system with the clinical and laboratory standards institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) Broth Microdilution Reference Methods and with the Sensititre YeastOne and Etest techniques for in vitro detection of antifungal resistance in yeast isolates. J Clin Microbiol 48(5):1782–1786
Fields GB, Noble RL (1990) Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int J Pept Protein Res 35(3):161–214
Finberg RW, Tally FP, Craig WA, West MA (2004) The importance of bactericidal drugs: future directions in infectious disease. Clin Infect Dis 39(9):1314–1320
Fitton JE, Dell A, Shaw WV (1980) The amino acid sequence of the delta haemolysin of Staphylococcus aureus. FEBS Lett 115(2):209–212
Fontana R, Mendes MA, Souza BMD, Konno K, César LLMM, Malaspina O, Palma MS (2004) Jelleines: a family of antimicrobial peptides from the Royal Jelly of honeybees (Apis mellifera). Peptides 25(6):919–928
Graybill JR, Najvar LK, Holmberg JD, Correa A, Luther MF (1995) Fluconazole treatment of Candida albicans infection in mice: does in vitro susceptibility predict in vivo response? Antimicrob Agents Chemother 39(10):2197–2200
Henderson-Begg SK, Sheppard CL, George RC, Livermore DM, Hall LMC (2010) Mutation frequency in antibiotic-resistant and -susceptible isolates of Streptococcus pneumoniae. Int J Antimicrob Agents 35(4):342–346
Hung C, Kao K, Wang P, Hu H, Hsieh MJ, Fu J, Chang C, Li L, Huang C, Tsai YH (2012) Invasive fungal infection among hematopoietic stem cell transplantation patients with mechanical ventilation in the intensive care unit. BMC Infect Dis 12(1):1–7
Iii LO, Soto AM, Knoop FC, Conlon JM (2001) Pseudin-2: an antimicrobial peptide with low hemolytic activity from the skin of the paradoxical frog. Biochem Biophys Res Commun 288(4):1001–1005
Ikeda F, Wakai Y, Matsumoto S, Maki K, Watabe E, Tawara S, Goto T, Watanabe Y, Matsumoto F, Kuwahara S (2000) Efficacy of FK463, a new lipopeptide antifungal agent, in mouse models of disseminated candidiasis and aspergillosis. Antimicrob Agents Chemother 44(3):619–621
Jang W, Kim HK, Lee KY, Kim SA, Han YS, Lee IH (2006) Antifungal activity of synthetic peptide derived from halocidin, antimicrobial peptide from the tunicate, Halocynthia aurantium. FEBS Lett 580(5):1490–1496
Jang WS, Bajwa JS, Sun JN, Edgerton M (2010) Salivary histatin 5 internalization by translocation, but not endocytosis, is required for fungicidal activity in Candida albicans. Mol Microbiol 77(2):354–370
Jovanovic N, Jovanovic J, Stefan-Mikic S, Kulauzov M, Aleksic-Dordevic M, Cvjetkovic D (2008) Mechanisms of bacterial resistance to antibiotics. Med Pregl 61(Suppl 1):9–14
Kassa J, Vachek J (2002) A comparison of the efficacy of pyridostigmine alone and the combination of pyridostigmine with anticholinergic drugs as pharmacological pretreatment of tabun-poisoned rats and mice. Toxicology 177(2–3):179–185
Khardori N, Nguyen H, Stephens LC, Kalvakuntla L, Rosenbaum B, Bodey GP (1993) Comparative efficacies of cilofungin (Ly121019) and amphotericin B against disseminated Candida albicans infection in normal and granulocytopenic mice. Antimicrob Agents Chemother 37(4):729–736
Koo JC, Lee B, Young ME, Koo SC, Cooper JA, Baek D, Lim CO, Lee SY, Yun D-J, Cho MJ (2004) Pn-AMP1, a plant defense protein, induces actin depolarization in yeasts. Plant Cell Physiol 45(11):1669–1680
Li Y (2009) Carrier proteins for fusion expression of antimicrobial peptides in Escherichia coli. Biotechnol Appl Biochem 54(1):1
Li Y, Zheng X, Cao Z, Xu W, Zhang J, Gong M (2012) Self-assembled peptide (CADY-1) improved the clinical application of doxorubicin. Int J Pharm 434(1–2):209–214
López-Rojas R, Docobo-Pérez F, Pachón-Ibáñez ME, Torre BGDL, Fernández-Reyes M, March C, Bengoechea JA, Andreu D, Rivas L, Pachón J (2011) Efficacy of cecropin A-melittin peptides on a sepsis model of infection by pan-resistant Acinetobacter baumannii. Eur J Clin Microbiol Infect Dis 30(11):1391–1398
Maccallum DM, Coste A, Ischer F, Jacobsen MD, Odds FC, Sanglard D (2010) Genetic dissection of azole resistance mechanisms in Candida albicans and their validation in a mouse model of disseminated infection. Antimicrob Agents Chemother 54(4):1476
Morassutti C, Amicis FD, Skerlavaj B, Zanetti M, Marchetti S (2002) Production of a recombinant antimicrobial peptide in transgenic plants using a modified VMA intein expression system. FEBS Lett 519(1–3):141–146
Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C (1991) A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods 139(2):271–279
Ostroskyzeichner L, Casadevall A, Galgiani JN, Odds FC, Rex JH (2010) An insight into the antifungal pipeline: selected new molecules and beyond. Nat Rev Drug Discov 9(9):719–727
Pag U, Oedenkoven M, Papo N, Oren Z, Shai Y, Sahl HG (2004) In vitro activity and mode of action of diastereomeric antimicrobial peptides against bacterial clinical isolates. J Antimicrob Chemother 53(2):230–239
Park S, Park SH, Ahn HC, Kim S, Kim SS (2001) Structural study of novel antimicrobial peptides, nigrocins, isolated from Rana nigromaculata. FEBS Lett 507(1):95–100
Pfaller MA, Jones RN, Doern GV, Sader HS, Hollis RJ, Messer SA (1998) International surveillance of bloodstream infections due to Candida species: frequency of occurrence and antifungal susceptibilities of isolates collected in 1997 in the United States, Canada, and South America for the SENTRY Program. The SENTRY Participan. J Clin Microbiol 36(7):1886–1889
Reddy K, Yedery RD, Aranha C (2004) Antimicrobial peptides: premises and promises. Int J Antimicrob Agents 24(6):536–547
Stgermain G, Laverdière M, Pelletier R, Bourgault AM, Libman M, Lemieux C, Noël G (2001) Prevalence and antifungal susceptibility of 442 Candida isolates from blood and other normally sterile sites: results of a 2-year (1996 to 1998) multicenter surveillance study in Quebec, Canada. J Clin Microbiol 39(3):949–953
Wang K, Yan J, Dang W, Xie J, Yan B, Yan W, Sun M, Zhang B, Ma M, Zhao Y (2014) Dual antifungal properties of cationic antimicrobial peptides polybia-MPI: membrane integrity disruption and inhibition of biofilm formation. Peptides 56:22–29
Wang K, Dang W, Xie J, Zhu R, Sun M, Jia F, Zhao Y, An X, Qiu S, Li X, Ma Z, Yan W, Wang R (2015) Antimicrobial peptide protonectin disturbs the membrane integrity and induces ROS production in yeast cells. Biochim Biophys Acta 1848(10 Pt A):2365–2373
Waxman DJ, Strominger JL (1983) Penicillin-binding proteins and the mechanism of action of beta-lactam antibiotics. Annu Rev Biochem 52:825–869
Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39(3):309–317
Yeaman MR, Bayer AS, Koo SP, Foss W, Sullam PM (1998) Platelet microbicidal proteins and neutrophil defensin disrupt the Staphylococcus aureus cytoplasmic membrane by distinct mechanisms of action. J Clin Investig 101(1):178
Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415(6870):389
Zhang L, Falla T, Wu M, Fidai S, Burian J, Kay W, Hancock RE (1998) Determinants of recombinant production of antimicrobial cationic peptides and creation of peptide variants in bacteria. Biochem Biophys Res Commun 247(3):674
Acknowledgements
We acknowledge the support of the funds from the National Natural Science Foundation of China (nos. 81573265, 91213302, 21272108, 81473095), the Chunhui Program of Ministry of Education of China (Z2016002), and the Fundamental Research Funds for the Central Universities (nos. lzujbky-2017-k11, lzujbky-2017-128).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declared that they have no conflicts of interest to this work.
Human participants
This article does not contain any studies with human participants performed by any of the authors.
Ethical standards
All procedures performed in studies involving animals were performed according to the ethical standards of Lanzhou University at which the studies were conducted.
Additional information
Handling Editor: J. González López.
Rights and permissions
About this article
Cite this article
Jia, F., Wang, J., Peng, J. et al. The in vitro, in vivo antifungal activity and the action mode of Jelleine-I against Candida species. Amino Acids 50, 229–239 (2018). https://doi.org/10.1007/s00726-017-2507-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-017-2507-1