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In vitro Activity of Monoclonal and Recombinant Yeast Killer Toxin-like Antibodies Against Antibiotic-resistant Gram-positive Cocci

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Abstract

Background

Monoclonal (mAbKT) and recombinant single-chain (scFvKT) anti-idiotypic antibodies were produced to represent the internal image of a yeast killer toxin (KT) characterized by a wide spectrum of antimicrobial activity, including Gram-positive cocci. Pathogenic eukaryotic and prokaryotic microorganisms, such as Candida albicans, Pneumocystis carinii, and a multidrug-resistant strain of Mycobacterium tuberculosis, presenting specific, although yet undefined, KT-cell wall receptors (KTR), have proven to be killed in vitro by mAbKT and scFvKT. mAbKT and scFvKT exert a therapeutic effect in vivo in experimental models of candidiasis and pneumocystosis by mimicking the functional activity of protective antibodies naturally produced in humans against KTR of infecting microorganisms. The swelling tide of concern over increasing bacterial resistance to antibiotic drugs gives the impetus to develop new therapeutic compounds against microbial threat. Thus, the in vitro bactericidal activity of mAbKT and scFvKT against gram-positive, drug-resistant cocci of major epidemiologial interest was investigated.

Materials and Methods

mAbKT and scFvKT generated by hybridoma and DNA recombinant technology from the spleen lymphocytes of mice immunized with a KT-neutralizing monoclonal antibody (mAb KT4) were used in a conventional colony forming unit (CFU) assay to determine, from a qualitative point of view, their bactericidal activity against Staphylococcus aureus, S. haemolyticus, Enterococcus faecalis, E. faecium, and Streptococcus pneumoniae strains. These bacterial strains are characterized by different patterns of resistance to antibiotics, including methicillin, vancomycin, and penicillin.

Results

According to the experimental conditions adopted, no bacterial isolate proved to be resistant to the activity of mAbKT and scFvKT.

Conclusions

scFvKT exerted a microbicidal activity against multidrug resistant bacteria, which may represent the basis for the drug modeling of new antibiotics with broad antibacterial spectra to tackle the emergence of microbial resistance.

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Acknowledgments

Ministero della Sanità, Istituto Superiore di Sanità, Programma Nazionale di Ricerca sull’AIDS—1998, Accordo di Collaborazione Scientifica n. 50B.32, and Ministero dell’Università e della Ricerca Scientifica e Tecnologica, Programmi di Ricerca Scientifica di Interesse Nazionale—1999.

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Authors and Affiliations

  1. Sezione di Microbiologia, Dipartimento di Patologia e Medicina di Laboratorio, Università degli Studi di Parma, Viale Antonio Gramsci, 14, 43100, Parma, Italy

    S. Conti, W. Magliani, S. Arseni, R. Frazzi, A. Salati &  L. Polonelli

  2. Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Ancona, Ancona, Italy

    P. E. Varaldo

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  1. S. Conti
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  2. W. Magliani
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Correspondence to L. Polonelli.

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Conti, S., Magliani, W., Arseni, S. et al. In vitro Activity of Monoclonal and Recombinant Yeast Killer Toxin-like Antibodies Against Antibiotic-resistant Gram-positive Cocci. Mol Med 6, 613–619 (2000). https://doi.org/10.1007/BF03401799

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