From <Emphasis Type="Italic">Pichia anomala</Emphasis> killer toxin through killer antibodies to killer peptides for a comprehensive anti-infective strategy |
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Authors: | Luciano Polonelli Walter Magliani Tecla Ciociola Laura Giovati Stefania Conti |
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Institution: | 1.Dipartimento di Patologia e Medicina di Laboratorio, Sezione di Microbiologia,Università degli Studi di Parma,Parma,Italy |
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Abstract: | “Antibiobodies”, antibodies (Abs) with antibiotic activity, internal image of a Pichia anomala killer toxin (PaKT) characterized by microbicidal activity against microorganisms expressing β-glucans cell-wall receptors (PaKTRs), were produced by idiotypic vaccination with a PaKT-neutralizing monoclonal Ab (PaKT-like Abs) or induced by a protein-conjugated β-glucan. Human natural PaKT-like Abs (PaKTAbs) were found in the vaginal fluid of women infected with KT-sensitive microorganisms. Monoclonal and recombinant PaKT-like Abs, and PaKTAbs proved to be protective against experimental candidiasis, cryptococcosis and aspergillosis. A killer decapeptide (KP),
synthesized from the sequence of a recombinant PaKT-like Ab or produced in transgenic plants, showed a microbicidal activity in vitro, neutralized by β-glucans, a therapeutic
effect in vivo, against experimental mucosal and systemic mycoses, and a prophylactic role in planta, against phytopathogenic microorganisms, respectively. KP showed fungicidal properties against all the defective mutants
of a Saccharomyces cerevisiae library, inclusive of strains recognized to be resistant to conventional antifungal drugs. KP inhibited in vitro, ex vivo
and/or in vivo HIV-1 and Influenza A virus replication, owing to down-regulation of CCR5 co-receptors, physical block of the
gp120-receptor interaction and reduction in the synthesis of glycoproteins, HA and M1 in particular. KP modulated the expression
of costimulatory and MHC molecules on murine dendritic cells, improving their capacity to induce lymphocyte proliferation.
KP, proven to be devoid of cytotoxicity on human cells, showed self-assembly-releasing hydrogel-like properties, catalyzed
by β 1,3 glucan. PaKT’s biotechnological derivatives may represent the prototypes of novel antifungal vaccines and anti-infective drugs characterized
by different mechanisms of action. |
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