Killer factor interference in mixed opportunistic yeast cultures

Conti, Stefania; Cantelli, C.; Gerloni, Mara; Fisicaro, Paola; Magliani, Walter; Bertolotti, Daniela; Mozzoni, Paola; Sullivan, Derek J.; Coleman, David C.; Polonelli, Luciano

doi:10.1007/bf00436568

Cited by 19 publications

(10 citation statements)

References 32 publications

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“…Although a therapeutically attractive tool for its wide spectrum of microbicidal activity in vitro, inclusive of such diverse pathogens as Candida albicans, Pneumocystis carinii, and Mycobacterium tuberculosis, KT is by itself of no practical use because of its instability in the physiological milieu of mammals as well as its antigenicity and toxicity (2,8,22,25). We postulated the possibility of exploiting KT antimicrobial activity without KT's undesired effects by mimicry through the Id network (4,14).…”

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confidence: 99%

Therapeutic Activity of an Engineered Synthetic Killer Antiidiotypic Antibody Fragment against Experimental Mucosal and Systemic Candidiasis

et al. 2003

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Peptides derived from the sequence of a single-chain, recombinant, antiidiotypic antibody (IdAb; KT-scFv) acting as a functional internal image of a microbicidal, wide-spectrum yeast killer toxin (KT) were synthesized and studied for their antimicrobial activity by using the KT-susceptible Candida albicans as model organism. A decapeptide containing the first three amino acids (SAS) of the light chain CDR1 was selected and optimized by alanine replacement of a single residue. This peptide exerted a strong candidacidal activity in vitro, with a 50% inhibitory concentration of 0.056 M, and was therefore designated killer peptide (KP). Its activity was neutralized by laminarin, a ␤1-3 glucan molecule, but not by pustulan, a ␤1-6 glucan molecule. KP also competed with the binding of a KT-like monoclonal IdAb to germinating cells of the fungus. In a rat model of vaginal candidiasis, local, postchallenge administration of KP was efficacious in rapidly abating infections caused by fluconazole-susceptible or -resistant C. albicans strains. In systemic infection of BALB/c or SCID mice preinfected intravenously with a lethal fungal load, KP caused a highly significant prolongation of the median survival time, with >80% of the animals still surviving after >60 days, whereas >90% of control mice died within 3 to 5 days. KP is therefore the first engineered peptide derived from a recombinant IdAb retaining KT microbicidal activity, probably through the interaction with the ␤-glucan KT receptor on target microbial cells.

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confidence: 99%

Therapeutic Activity of an Engineered Synthetic Killer Antiidiotypic Antibody Fragment against Experimental Mucosal and Systemic Candidiasis

et al. 2003

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“…The 50× concentrated KT, to be used as reference antigen in ELISA, was tested for killer activity by a conventional well assay against C. albicans UP10S, employed as reference KT-susceptible strain throughout the study [20].…”

Section: Methodsmentioning

confidence: 99%

“…The in vitro candidacidal activity of the selected mAb and sera from immunized animals against C. albicans UP10S were carried out by conventional colony forming unit (CFU) assays [20]. Briefly, 10 µl of H 2 O containing ∼2–3×10 2 germinating yeast cells (expected number of CFU in the controls) were added to 90 µl of H 2 O in the presence or absence (control growth) of the purified mAb (final concentration 100 µg) or different dilutions of sera from immunized animals.…”

Section: Methodsmentioning

confidence: 99%

Yeast Killer Toxin-Like Candidacidal Ab6 Antibodies Elicited through the Manipulation of the Idiotypic Cascade

et al. 2014

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A mouse anti-anti-anti-idiotypic (Id) IgM monoclonal antibody (mAb K20, Ab4), functionally mimicking a Wyckerhamomyces anomalus (Pichia anomala) killer toxin (KT) characterized by fungicidal activity against yeasts presenting specific cell wall receptors (KTR) mainly constituted by β-1,3-glucan, was produced from animals presenting anti-KT Abs (Ab3) following immunization with a rat IgM anti-Id KT-like mAb (mAb K10, Ab2). MAb K10 was produced by immunization with a KT-neutralizing mAb (mAb KT4, Ab1) bearing the internal image of KTR. MAb K20, likewise mAb K10, proved to be fungicidal in vitro against KT-sensitive Candida albicans cells, an activity neutralized by mAb KT4, and was capable of binding to β-1,3-glucan. MAb K20 and mAb K10 competed with each other and with KT for binding to C. albicans KTR. MAb K20 was used to identify peptide mimics of KTR by the selection of phage clones from random peptide phage display libraries. Using this strategy, four peptides (TK 1-4) were selected and used as immunogen in mice in the form of either keyhole limpet hemocyanin (KLH) conjugates or peptide-encoding minigenes. Peptide and DNA immunization could induce serum Abs characterized by candidacidal activity, which was inhibited by laminarin, a soluble β-1,3-glucan, but not by pustulan, a β-1,6-glucan. These findings show that the idiotypic cascade can not only overcome the barrier of animal species but also the nature of immunogens and the type of technology adopted.

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“…Several studies have shown that killer yeasts are more abundant in natural habitats than in culture collections. It has been postulated that this may be due to the advantage that killer yeasts may have over sensitive strains in mixed cultures (Young, 1987; Conti et al , 1996; Marquina et al , 2002; Golubev, 2006). In addition, since some killer toxins are encoded by extra‐chromosomal DNA or RNA (plasmids), it is possible that these are lost during many cycles of cell proliferation in the laboratory environment (Fukuhara, 1995; Schmitt & Breinig, 2002; Golubev, 2006).…”

Section: The Use Of Ksps As a Yeast Biotyping Tool: Ecological Implicmentioning

confidence: 99%

The use of killer sensitivity patterns for biotyping yeast strains: the state of the art, potentialities and limitations

Buzzini

Turchetti

Vaughan-Martini

2007

FEMS Yeast Research

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In recent years molecular techniques have been the most useful tools for the unequivocal identification of undetermined strains at the species level. In many instances, however, a further discrimination at the strain level (biotyping) is required, such as during epidemiological investigations, in which the distribution of pathogenic microorganisms is studied, and for patent protection purposes. Although molecular methods are routinely used also for yeast biotyping, several nonmolecular techniques have been proposed. One of these, the determination of the killer sensitivity pattern (KSP) towards a panel of selected killer toxins has proven to be a good auxiliary method. Despite the plethora of studies published, the potential and limitations of the determination of KSPs have never been critically evaluated. In this review the use of this nonmolecular technique as a biotyping tool is discussed and compared with some currently used DNA-based procedures. In addition, methodological, mechanistic and ecological implications are evaluated.

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Killer factor interference in mixed opportunistic yeast cultures

Cited by 19 publications

References 32 publications

Therapeutic Activity of an Engineered Synthetic Killer Antiidiotypic Antibody Fragment against Experimental Mucosal and Systemic Candidiasis

Therapeutic Activity of an Engineered Synthetic Killer Antiidiotypic Antibody Fragment against Experimental Mucosal and Systemic Candidiasis

Yeast Killer Toxin-Like Candidacidal Ab6 Antibodies Elicited through the Manipulation of the Idiotypic Cascade

The use of killer sensitivity patterns for biotyping yeast strains: the state of the art, potentialities and limitations

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