From yeast killer toxins to antibiobodies and beyond

Abstract

Antibiobodies are paradigmatic of yeast killer toxin (KT)-like antibodies (KAbs) mimicking the antimicrobial activity of KTs in the frame of the yeast killer phenomenon. Polyclonal, monoclonal and recombinant anti-idiotypic antibiobodies (anti-idiotypic KAbs), internal images of a wide-spectrum KT produced by the yeast Pichia anomala (PaKT), have been produced by immunization with the idiotype of a PaKT-neutralizing monoclonal antibody. Anti-idiotypic KAbs showed microbicidal activity against eukaryotic and prokaryotic pathogenic agents through the interaction with specific KT receptors (KTRs), putatively constituted by beta-glucans. Natural KAbs have been found in animals and humans experimentally or naturally infected by KTR-bearing microorganisms. Recombinant KAb-derived synthetic killer peptides showed further antiviral and immunomodulatory activities. The perspectives of KAbs and killer peptides as potential sources of novel therapeutic agents, and of KTRs and idiotypes as vaccines against infectious diseases are discussed.

Antibody-Dependent Cell-Mediated Cytotoxicity- and Complement-Dependent Cytotoxicity-Independent Bactericidal Activity of an IgG against Pseudomonas aeruginosa O6ad

“…A subset of killer toxin-like Abs (KT-Abs), produced by idiotypic vaccination with mAb KT4 that was raised to neutralize a KT produced by Pichia anomala, showed broad antimicrobial activities in vitro against pathogenic bacteria, protozoa, and fungi (3,35) and provided protection in experimental models of local and systemic fungal infections (36,37). These Abs functionally mimic the cytotoxic action of the P. anomala KT, which has wide-spectrum antimicrobial activity against prokaryotic and eukaryotic microorganisms presenting receptors for KT (38). Similar activities were observed with KT-mAb and its recombinant KT-scFv (3,(35)(36)(37)39).…”

Disruption of the Gene Encoding β-1, 3-Glucanase in Marine-Derived Williopsis saturnus WC91-2 Enhances its Killer Toxin Activity

“…It has been shown that the killer toxin produced by W. saturnus has many applications (Magliani et al 2008). In order to increase the activity of the killer toxin, it is necessary to disrupt the WsEXG1 gene in W. saturnus WC91-2.…”

“…To date, the toxin-producing killer yeasts have been identified in the genera Candida, Cryptococcus, Debaryomyces, Hanseniaspora, Hansenula, Kluyveromyces, Metschnikowia, Pichia, Saccharomyces, Ustilago, Torulopsis, Williopsis, Mrakia, and Zygosaccharomyces, indicating that the killer phenomenon is indeed widespread among yeasts (Magliani et al 1997;Hua et al 2010). Among them, the killer toxins produced by different species of Williopsis and Pichia have received increasing attention because they can kill a wide range of sensitive microorganisms including the pathogenic Candida albicans and some filamentous fungi and bacteria (Magliani et al 2008). Much research has shown that killer yeasts can be applied to control the growth of pathogenic yeasts in humans, animals, and plants .…”

Mycoviruses: future therapeutic agents of invasive fungal infections in humans?

“…However, although some researchers have shown that topical applications in the treatment of superficial lesions might well be possible, one drawback of most yeast killer proteins is that they exhibit their cytotoxic activity only at temperatures between 20°C and 30°C within a narrow pH range [53,54]. Therefore, yeast toxins are unsuitable as direct applications for oral and/or intravenous administration [55]. Killer toxins, however, fuelled the development of new antifungal agents that mimick the antimicrobial activity of killer toxins, so-called killer antibodies and killer antibodyderived peptides.…”

“…These derivatives have shown activity against various human fungal pathogenic fungi including C. albicans and may be therapeutic when administered parentally. For reviews of killer toxin/antibodies the reader is referred to Marquina et al [49], Magliani et al [55], and Schmitt and Breinig [40].…”