Synthetic peptides with sequences identical to fragments of the constant region of different classes (IgG, IgM, IgA) of antibodies (Fc-peptides) exerted a fungicidal activity in vitro against pathogenic yeasts, such as Candida albicans, Candida glabrata, Cryptococcus neoformans, and Malassezia furfur, including caspofungin and triazole resistant strains. Alanine-substituted derivatives of fungicidal Fc-peptides, tested to evaluate the critical role of each residue, displayed unaltered, increased or decreased candidacidal activity in vitro. An Fc-peptide, included in all human IgGs, displayed a therapeutic effect against experimental mucosal and systemic candidiasis in mouse models. It is intriguing to hypothesize that some Fc-peptides may influence the antifungal immune response and constitute the basis for devising new antifungal agents.
References
[1]
Cohen S, Porter RB (1964) Structure and biological activity of immunoglobulins. Advances in Immunology 27: 287–349.
[2]
Polonelli L, Magliani W, Conti S, Bracci L, Lozzi L, et al. (2003) Therapeutic activity of an engineered synthetic killer antiidiotypic antibody fragment against experimental mucosal and systemic candidiasis. Infection and Immunity 71: 6205–6212.
[3]
Magliani W, Conti S, Cunha RLOR, Travassos LR, Polonelli L (2009) Antibodies as crypts of antiinfective and antitumor peptides. Current Medicinal Chemistry 16: 2305–2323.
[4]
Pertinhez TA, Conti S, Ferrari E, Magliani W, Spisni A, et al. (2009) Reversible self-assembly: a key feature for a new class of autodelivering therapeutic peptides. Molecular Pharmaceutics 6: 1036–1039.
[5]
Polonelli L, Ponton J, Elguezabal N, Moragues MD, Casoli C, et al. (2008) Antibody Complementarity-Determining Regions (CDRs) can display differential antimicrobial, antiviral and antitumor activities. PLoS One 3: e2371.
[6]
Bistoni F, Vecchiarelli A, Cenci E, Puccetti P, Marconi P, et al. (1986) Evidence for macrophage-mediated protection against lethal Candida albicans infection. Infection and Immunity 51: 668–674.
[7]
Singh NP, McCoy MT, Tice RR, Sheider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental Cell Research 237: 123–130.
[8]
Tortorano AM, Kibbler C, Peman J, Bernhardt H, Klingspor L, et al. (2006) Candidaemia in Europe: epidemiology and resistance. International Journal of Antimicrobial Agents 27: 359–366.
[9]
Pappas PG, Alexander BD, Andes DR, Hadley S, Kauffman CA, et al. (2010) Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clinical Infectious Diseases 50: 1101–1111.
[10]
Leventakos K, Lewis RE, Kontoyiannis DP (2010) Fungal infections in leukemia patients: how do we prevent and treat them? Clinical Infectious Diseases 50: 405–415.
[11]
De Smet K, Contreras R (2005) Human antimicrobial peptides: defensins, cathelicidins and histatins. Biotechnology Letters 27: 1337–1347.
Hancock REW, Sahl HG (2006) Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nature Biotechnology 24: 1551–1557.
[14]
Wang GS, Li X, Wang Z (2009) APD2: the updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Research 37: D933–D937.
[15]
Cenci E, Pericolini E, Mencacci A, Conti S, Magliani W, et al. (2006) Modulation of phenotype and function of dendritic cells by a therapeutic synthetic killer peptide. Journal of Leukocyte Biology 79: 40–45.
[16]
Gabrielli E, Pericolini E, Cenci E, Ortelli F, Magliani W, et al. (2009) Antibody Complementarity-Determining Regions (CDRs): a bridge between adaptive and innate immunity. PLoS One 4: e8187. doi:10.1371/journal.pone.0008187.
Autelitano DJ, Rajic A, Smith AI, Berndt MC, Ilag LL, et al. (2006) The cryptome: a subset of the proteome, comprising cryptic peptides with distinct bioactivities. Drug Discovery Today 11: 306–314.
[19]
Ng JH, Ilag LL (2006) Cryptic protein fragments as an emerging source of peptide drugs. IDrugs: the investigational drugs journal 9: 343–346.
[20]
Pimenta DC, Lebrun I (2007) Cryptides: buried secrets in proteins. Peptides 28: 2403–2410.
[21]
Ueki N, Someya K, Matsuo Y, Wakamatsu K, Mukai H (2007) Cryptides: functional cryptic peptides hidden in protein structures. Biopolymers 88: 190–198.
[22]
Samir P, Link AJ (2011) Analyzing the cryptome: uncovering secret sequences. AAPS Journal 13: 152–158.
