Rediscovery of antimicrobial peptides as therapeutic agents

다국어 초록 (Multilingual Abstract)

In recent years, the occurrence of antibiotic-resistant pathogens is increasing rapidly. There is growing concern as the development of antibiotics is slower than the increase in the resistance of pathogenic bacteria. Antimicrobial peptides (AMPs) are promising alternatives to antibiotics. Despite their name, which implies their antimicrobial activity, AMPs have recently been rediscovered as compounds having antifungal, antiviral, anticancer, antioxidant, and insecticidal effects.
Moreover, many AMPs are relatively safe from toxic side effects and the generation of resistant microorganisms due to their target specificity and complexity of the mechanisms underlying their action. In this review, we summarize the history, classification, and mechanisms of action of AMPs, and provide descriptions of AMPs undergoing clinical trials. We also discuss the obstacles associated with the development of AMPs as therapeutic agents and recent strategies formulated to circumvent these obstacles.

참고문헌 (Reference)

1 bilal shaker, "User guide for the discovery of potential drugs via protein structure prediction and ligand docking simulation" 한국미생물학회 58 (58): 235-244, 2020

2 Chan, D. I., "Tryptophan-and arginine-rich antimicrobial peptides : structures and mechanisms of action" 1758 : 1184-1202, 2006

3 Chalekson, C. P., "Treatment of infected wounds with the antimicrobial peptide D2A21" 54 : 770-774, 2003

4 Rammelkamp, C. H., "Toxic effects of tyrothricin, gramicidin and tyrocidine" 71 : 166-173, 1942

5 Pal, S., "Towards the synthesis of sugar amino acid containing antimicrobial noncytotoxic CAP conjugates with gold nanoparticles and a mechanistic study of cell disruption" 9 : 4806-4810, 2011

6 강희경, "The therapeutic applications of antimicrobial peptides (AMPs): a patent review" 한국미생물학회 55 (55): 1-12, 2017

7 Xhindoli, D., "The human cathelicidin LL-37 – A poreforming antibacterial peptide and host-cell modulator" 1858 : 546-566, 2016

8 Nguyen, L. T., "The expanding scope of antimicrobial peptide structures and their modes of action" 29 : 464-472, 2011

9 Dubos, R. J., "The effect of specific agents extracted from soil microorganisms upon experimental bacterial infections" 13 : 2025-2037, 1940

10 Lemaitre, B., "The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults" 86 : 973-983, 1996

11 Hirano, S., "The blood compatibility of chitosan and N-acylchitosans" 19 : 413-417, 1985

12 Lei, J., "The antimicrobial peptides and their potential clinical applications" 11 : 3919-3931, 2019

13 Mak, A. S., "The amino acid sequence of wheat β-purothionin" 54 : 835-842, 1976

14 Saravolatz, L. D., "Telavancin : a novel lipoglycopeptide" 49 : 1908-1914, 2009

15 Vincent, J. L., "Talactoferrin in severe sepsis : Results from the phase II/III oral tAlactoferrin in severe sepsis trial" 43 : 1832-1838, 2015

16 Usmani, S. S., "THPdb : Database of FDA-approved peptide and protein therapeutics" 12 : e0181748-, 2017

17 Tuerk, C., "Systematic evolution of ligands by exponential enrichment : RNA ligands to bacteriophage T4 DNA polymerase" 249 : 505-510, 1990

18 Chen, R., "Synthesis, characterization and in vitro activity of a surface-attached antimicrobial cationic peptide" 25 : 517-524, 2009

19 Lupetti, A., "Synergistic activity of the N-terminal peptide of human lactoferrin and fluconazole against Candida species" 47 : 262-267, 2003

20 Dubos, R. J., "Studies on a bactericidal agent extracted from a soil Bacillus : II. Protective effect of the bactericidal agent against experimental Pneumococcus infections in mice" 70 : 11-17, 1939

21 Dubos, R. J., "Studies on a bactericidal agent extracted from a soil Bacillus : I. Preparation of the agent. Its activity in vitro" 70 : 1-10, 1939

22 Babii, O., "Structure–activity relationships of photoswitchable diarylethene-based β-hairpin peptides as membranolytic antimicrobial and anticancer agents" 61 : 10793-10813, 2018

23 Klüver, E., "Structure-activity relation of human β-defensin 3 : influence of disulfide bonds and cysteine substitution on antimicrobial activity and cytotoxicity" 44 : 9804-9816, 2005

24 Tang, M., "Structure and mechanism of β-hairpin antimicrobial peptides in lipid bilayers from solid-state NMR spectroscopy" 5 : 317-322, 2009

25 Takahashi, D., "Structural determinants of host defense peptides for antimicrobial activity and target cell selectivity" 92 : 1236-1241, 2010

26 Porciatti, E., "Structural characterization and antimicrobial activity of the Zn(II) complex with P113(Demegen), a derivative of histatin 5" 49 : 8690-8698, 2010

27 Wang, F., "Solubilized gramicidin A as potential systemic antibiotics" 13 : 51-55, 2012

28 Steiner, H., "Sequence and specificity of two antibacterial proteins involved in insect immunity" 292 : 246-248, 1981

29 Kaplan, C. W., "Selective membrane disruption: mode of action of C16G2, a specifically targeted antimicrobial peptide" 55 : 3446-3452, 2011

30 Huang, Y. B., "Role of helicity on the anticancer mechanism of action of cationic-helical peptides" 13 : 6849-6862, 2012

31 Calhoun, D. M., "Role of antimicrobial peptides in amphibian defense against trematode infection" 13 : 383-391, 2016

32 Li, Z., "Research advances on plectasin and its derivatives as new potential antimicrobial candidates" 56 : 62-70, 2017

33 Van Epps, H. L., "René Dubos : unearthing antibiotics" 203 : 259-, 2006

34 Schroeder, B. O., "Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1" 469 : 419-423, 2011

35 Ron-Doitch, S., "Reduced cytotoxicity and enhanced bioactivity of cationic antimicrobial peptides liposomes in cell cultures and 3D epidermis model against HSV" 229 : 163-171, 2016

36 Li, Y., "Recombinant production of antimicrobial peptides in Escherichia coli : a review" 80 : 260-267, 2011

37 Selsted, M. E., "Purification, primary structures, and antibacterial activities of β-defensins, a new family of antimicrobial peptides from bovine neutrophils" 268 : 6641-6648, 1993

38 Selsted, M. E., "Purification and antibacterial activity of antimicrobial peptides of rabbit granulocytes" 45 : 150-154, 1984

39 Selsted, M. E., "Primary structures of MCP-1 and MCP-2, natural peptide antibiotics of rabbit lung macrophages" 258 : 14485-14489, 1983

40 Mygind, P. H., "Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus" 437 : 975-980, 2005

41 Niemeyer-van der Kolk, T., "Pharmacodynamic effects of topical omiganan in patients with mild to moderate atopic dermatitis in a randomized, placebo-controlled, phase II trial" 13 : 994-1003, 2020

42 Lamb, H. M., "Pexiganan acetate" 56 : 1047-1052, 1998

43 Lee, J. H., "Perspectives towards antibiotic resistance : from molecules to population" 57 : 181-184, 2019

44 Li, P., "Oral delivery of peptides and proteins using lipid-based drug delivery systems" 9 : 1289-1304, 2012

45 Rai, A., "One-step synthesis of high-density peptide-conjugated gold nanoparticles with antimicrobial efficacy in a systemic infection model" 85 : 99-110, 2016

46 Fleming, A., "On a remarkable bacteriolytic element found in tissues and secretions" 93 : 306-317, 1922

47 Grieco, P., "Novel α-melanocyte stimulating hor-mone peptide analogues with high candidacidal activity" 46 : 850-855, 2003

48 Mankelow, D. P., "Non-ribosomal peptide antibiotics" 10 : 1583-1591, 2000

49 Zhanel, G. G., "New Lipoglycopeptides" 70 : 859-886, 2010

50 Mercer, D. K., "NP213(NovexatinŠ) : A unique therapy candidate for onychomycosis with a differentiated safety and efficacy profile" 58 : 1064-1072, 2020

51 Townsend, D. M., "NOV-002, a glutathione disulfide mimetic, as a modulator of cellular redox balance" 68 : 2870-2877, 2008

52 Etienne, O., "Multilayer polyelectrolyte films functionalized by insertion of defensin : a new approach to protection of implants from bacterial colonization" 48 : 366-3669, 2004

53 Lee, E. Y., "Modulation of tolllike receptor signaling by antimicrobial peptides" 88 : 173-184, 2019

54 Héchard, Y., "Mode of action of modified and unmodified bacteriocins from Gram-positive bacteria" 84 : 545-557, 2002

55 Shai, Y., "Mode of action of membrane active antimicrobial peptides" 66 : 236-248, 2002

56 Riedl, S., "Membrane-active host defense peptides–challenges and perspectives for the development of novel anticancer drugs" 164 : 766-781, 2011

57 Catania, A., "Melanocortin peptides inhibit production of proinflammatory cytokines in blood of HIV-infected patients" 19 : 1099-1104, 1998

58 Park, C. B. Kim, H. S., "Mechanism of action of the antimicrobial peptide buforin II : buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions" 244 : 253-257, 1998

59 Pirri, G., "Lipopeptides as anti-infectives : a practical perspective" 4 : 258-273, 2009

60 Breukink, E., "Lipid II as a target for antibiotics" 5 : 321-323, 2006

61 Wimley, W. C., "Interactions between human defensins and lipid bilayers : evidence for formation of multimeric pores" 3 : 1362-1373, 1994

62 Hultmark, D., "Insect immunity. Purification and properties of three inducible bactericidal proteins from hemolymph of immunized pupae of Hyalophora cecropia" 106 : 7-16, 1980

63 Wu, Q., "Insect antimicrobial peptides, a mini review" 10 : 461-, 2018

64 Ellington, A. D., "In vitro selection of RNA molecules that bind specific ligands" 346 : 818-822, 1990

65 Saravolatz, L. D., "In vitro activities of LTX-109, a synthetic antimicrobial peptide, against methicillin-resistant, vancomycin-intermediate, vancomycin-resistant, daptomycin-nonsusceptible, and linezolid-nonsusceptible Staphylococcus aureus" 56 : 4478-4482, 2012

66 Sur, A., "Immune activation efficacy of indolicidin is enhanced upon conjugation with carbon nanotubes and gold nanoparticles" 10 : e0123905-, 2015

67 Begley, M., "Identification of a novel two-peptide lantibiotic, lichenicidin, following rational genome mining for LanM proteins" 75 : 5451-5460, 2009

68 Sass, V., "Human β-defensin 3 inhibits cell wall biosynthesis in Staphylococci" 78 : 2793-2800, 2010

69 Nibbering, P. H., "Human lactoferrin and peptides derived from its N terminus are highly effective against infections with antibiotic-resistant bacteria" 69 : 1469-1476, 2001

70 Khan, N. A., "Human chorionic gonadotropin : a model molecule for oligopeptide-based drug discovery" 11 : 32-53, 2011

71 Sørensen, O. E., "Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3." 97 : 3951-3959, 2001

72 Papo, N., "Host defense peptides as new weapons in cancer treatment" 62 : 784-790, 2005

73 Mansour, S. C., "Host defense peptides : front-line immunomodulators" 35 : 443-450, 2014

74 Kavanagh, K., "Histatins : antimicrobial peptides with therapeutic potential" 56 : 285-289, 2004

75 Soundrarajan, N., "Green fluorescent protein as a scaffold for high efficiency production of functional bacteriotoxic proteins in Escherichia coli" 6 : 20661-, 2016

76 Gause, G. F., "Gramicidin S and its use in the treatment of infected wounds" 154 : 703-, 1944

77 Yeom, J. H., "Gold nanoparticle-DNA aptamer conjugate-assisted delivery of antimicrobial peptide effectively eliminates intracellular Salmonella enterica serovar Typhimurium" 104 : 43-51, 2016

78 de Leeuw, E., "Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II" 584 : 1543-1548, 2010

79 Gaspar, D., "From antimicrobial to anticancer peptides. A review" 4 : 294-, 2013

80 Agerberth, B., "FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis" 92 : 195-199, 1995

81 Pal, I., "Enhanced stability and activity of an antimicrobial peptide in conjugation with silver nanoparticle" 483 : 385-393, 2016

82 Wu, Z., "Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human β-defensin 3" 100 : 8880-8885, 2003

83 Hilchie, A., "Emerging Cancer Therapy" John Wiley &Sons 309-332, 2010

84 Cunningham, F. E., "Egg-white lysozyme as a food preservative : an overview" 47 : 141-163, 1991

85 Doherty, T., "Dynamic structure of disulfide-removed linear analogs of tachyplesin-I in the lipid bilayer from solid-state NMR" 47 : 1105-1116, 2008

86 Tucker, A. T., "Discovery of next-generation antimicrobials through bacterial self-screening of surface-displayed peptide libraries" 172 : 618-628, 2018

87 McClerren, A. L., "Discovery and in vitro; biosynthesis of haloduracin, a two-component lantibiotic" 103 : 17243-17248, 2006

88 Wimley, W. C., "Describing the mechanism of antimicrobial peptide action with the interfacial activity model" 5 : 905-917, 2010

89 Ganz, T., "Defensins. Natural peptide antibiotics of human neutrophils" 76 : 1427-1435, 1985

90 Carpenter, C. F., "Daptomycin : another novel agent for treating infections due to drug-resistant Grampositive pathogens" 38 : 994-1000, 2004

91 Chen, A. Y., "Dalbavancin : a novel antimicrobial" 61 : 853-863, 2007

92 Kang, X., "DRAMP 2.0, an updated data repository of antimicrobial peptides" 6 : 148-, 2019

93 Pirtskhalava, M., "DBAASP v. 2 : an enhanced database of structure and antimicrobial/cytotoxic activity of natural and synthetic peptides" 44 : D1104-D1112, 2016

94 Hill, C. P., "Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization" 251 : 1481-1485, 1991

95 Costa, F., "Covalent immobilization of antimicrobial peptides(AMPs)onto biomaterial surfaces" 7 : 1431-1440, 2011

96 Bommarius, B., "Cost-effective expression and purification of antimicrobial and host defense peptides in Escherichia coli" 31 : 1957-1965, 2010

97 Ohtani, S., "Complete primary structures of two subunits of purothionin A, a lethal protein for brewer’s yeast from wheat flour" 82 : 753-767, 1977

98 Lee, M. T., "Comparison of the effects of daptomycin on bacterial and model membranes" 57 : 5629-5639, 2018

99 Faber, C., "Comparable efficacies of the antimicrobial peptide human lactoferrin 1-11 and gentamicin in a chronic methicillin-resistant Staphylococcus aureus osteomyelitis model" 49 : 2438-2444, 2005

100 Chandy, T., "Chitosan-as a biomaterial" 18 : 1-24, 1990

101 Piras, A. M., "Chitosan nanoparticles loaded with the antimicrobial peptide temporin B exert a long-term antibacterial activity in vitro against clinical isolates of Staphylococcus epidermidis" 6 : 372-, 2015

102 Hancock, R. E., "Cationic antimicrobial peptides : towards clinical applications" 9 : 1723-1729, 2000

103 Cotter, P. D., "Bacteriocins-a viable alternative to antibiotics?" 11 : 95-105, 2013

104 Epand, R. M., "Bacterial membrane lipids in the action of antimicrobial agents" 17 : 298-305, 2011

105 Kong, M., "Antimicrobial properties of chitosan and mode of action : A state of the art review" 144 : 51-63, 2010

106 Brogden, K. A., "Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?" 3 : 238-250, 2005

107 Kumar, P., "Antimicrobial peptides: diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo" 8 : 4-, 2018

108 Wang, G, "Antimicrobial peptides: Discovery, design, and novel therapeutic strategies" CABI Publishing 2010

109 Greber, K. E., "Antimicrobial peptides under clinical trials" 17 : 620-628, 2017

110 Martin, L., "Antimicrobial peptides in human sepsis" 6 : 404-, 2015

111 Zhang, L., "Antimicrobial peptides : therapeutic potential" 7 : 653-663, 2006

112 Bahar, A. A., "Antimicrobial peptides" 6 : 1543-1575, 2013

113 Lee, B., "Antimicrobial peptide-loaded gold nanoparticle-DNA aptamer conjugates as highly effective antibacterial therapeutics against Vibrio vulnificus" 7 : 13572-, 2017

114 Laverty, G., "Antimicrobial peptide incorporated poly(2-hydroxyethyl methacrylate)hydrogels for the prevention of Staphylococcus epidermidis-associated biomaterial infections" 100 : 1803-1814, 2012

115 Benkerroum, N., "Antimicrobial activity of lysozyme with special relevance to milk" 725 : 4856-4867, 2009

116 Mathew, B., "Antimicrobial activity of human α-defensin 5 and its linear analogs : N-terminal fatty acylation results in enhanced antimicrobial activity of the linear analogs" 71 : 128-140, 2015

117 Phoenix, D., "Antimicrobial Peptides" Wiley‐VCH Verlag GmbH & Co. KGaA 1-37, 2013

118 Jenssen, H., "Antimicrobial Peptides" Humana Press 329-347, 2010

119 Fennell, J. F., "Antibacterial action of a bee venom fraction (melittin) against a penicillin-resistant Staphylococcus and other microorganisms. USNRDL-TR67-101" 5 : 1-13, 1967

120 Li, J., "Anti-infection peptidomics of amphibian skin" 6 : 882-894, 2007

121 Scott, M. G., "An anti-infective peptide that selectively modulates the innate immune response" 25 : 465-472, 2007

122 Wiegand, I., "Agar and broth dilution methods to determine the minimal inhibitory concentration(MIC)of antimicrobial substances" 3 : 163-175, 2008

123 Kollef, M., "A randomized double-blind trial of iseganan in prevention of ventilator-associated pneumonia" 173 : 91-97, 2006

124 Giles, F. J., "A phase III, randomized, double-blind, placebocontrolled, study of iseganan for the reduction of stomatitis in patients receiving stomatotoxic chemotherapy" 28 : 559-565, 2004

125 Trotti, A., "A multinational, randomized phase III trial of iseganan HCl oral solution for reducing the severity of oral mucositis in patients receiving radiotherapy for head-and-neck malignancy" 58 : 674-681, 2004

126 Tang, Y. Q., "A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated α-defensins" 286 : 498-502, 1999