Mycobactericidal activity of human natural, monoclonal, and recombinant yeast killer toxin-like antibodies.

Human natural (KTAb), murine monoclonal (KTMAb), and single-chain recombinant (KTScFv) candidacidal antibodies representing the internal image of a killer toxin from the yeast Pichia anomala (KT), characterized by a wide spectrum of antibiotic activity, exerted a lethal effect against a KT-sensitive multidrug-resistant isolate of Mycobacterium tuberculosis. KTMAb and KTScFv were produced by the hybridoma and DNA technologies, respectively, from the spleen lymphocytes of animals immunized with the idiotype of a KT-neutralizing MAb (MAb KT4), while KTAb were purified against MAb KT4 from the vaginal fluid of women infected with Candida albicans cells bearing an idiotype-like KT cell wall receptor. Mycobactericidal activity was related to the binding of KTAb, KTMAb, and KTScFv to the cell surface of KT-sensitive bacterial cells and was prevented by specific absorption of KT-like antibodies onto MAb KT4. These data identify a novel potentially useful immunotherapeutic approach to tuberculosis.

Yeast killer systems.

The killer phenomenon in yeasts has been revealed to be a multicentric model for molecular biologists, virologists, phytopathologists, epidemiologists, industrial and medical microbiologists, mycologists, and pharmacologists. The surprisingly widespread occurrence of the killer phenomenon among taxonomically unrelated microorganisms, including prokaryotic and eukaryotic pathogens, has engendered a new interest in its biological significance as well as its theoretical and practical applications. The search for therapeutic opportunities by using yeast killer systems has conceptually opened new avenues for the prevention and control of life-threatening fungal diseases through the idiotypic network that is apparently exploited by the immune system in the course of natural infections. In this review, the biology, ecology, epidemiology, therapeutics, serology, and idiotypy of yeast killer systems are discussed.

Monoclonal yeast killer toxin-like candidacidal anti-idiotypic antibodies.

Rat monoclonal yeast killer toxin (KT)-like immunoglobulin M (IgM) anti-idiotypic antibodies (KT-IdAbs) were produced by idiotypic vaccination with a mouse monoclonal antibody (MAb; MAb KT4) that neutralized a Pichia anomala KT characterized by a wide spectrum of antimicrobial activity. The characteristics of the KT-IdAbs were demonstrated by their capacity to compete with the KT to the idiotype of MAb KT4 and to interact with putative KT cell wall receptors (KTRs) of sensitive Candida albicans cells. The internal-image properties of KT-IdAbs were proven by their killer activity against KT-sensitive yeasts. This lethal effect was abolished by prior adsorption of KT-IdAbs with MAb KT4. These findings stressed the potential importance of antibody-mediated immunoprotection against candidiasis and suggested a feasible experimental approach for producing antimicrobial receptor antibodies without purifying the receptor. KT-IdAbs might represent the basis for producing engineered derivatives with a high potential for effective therapeutic antifungal activity.

Therapeutic potential of antiidiotypic single chain antibodies with yeast killer toxin activity.

Single chain fragment (ScFv) antiidiotypic antibodies (antilds) of a killer toxin (KT) from the yeast Pichia anomala have been produced by recombinant DNA methodology from the splenic lymphocytes of mice immunized by idiotypic vaccination with a KT-neutralizing monoclonal antibody (Mab KT4). ScFv KT-like antilds (KTIdAb) react with specific Candida albicans KT cell wall receptors (KTR) exerting a candidacidal activity in vitro could be neutralized by adsorption with Mab KT4. ScFv KTIdAb displayed an effective therapeutic activity in an experimental model of rat candidal vaginitis.

Killer factor interference in mixed opportunistic yeast cultures.

The interaction of the killer yeast Pichia anomala UP 25F with the killer toxin-sensitive clinical isolate Candida albicans UCSC 10S and its natural toxin-resistant mutant derivative C. albicans UCSC 10R were studied under various conditions. A differential inhibition was shown to occur in vitro at pH and temperature values, which are not encountered in vivo, only by using preformed killer toxin, since antagonism due to yeast growth proved to be predominant on the killer effect. Under adverse growth conditions, the P. anomala killer yeast proved to be able to produce an anatoxin antigenically related to the active or heat inactivated killer toxin. These findings suggest that killer toxins may not function as potential virulence factors in the competition between the opportunistic killer yeast P. anomala and sensitive microorganisms for colonization in the course of natural human infections.