In vitro activity of monoclonal and recombinant yeast killer toxin-like antibodies against antibiotic-resistant gram-positive cocci

Background: Monoclonal (mAbKT) and recombinant single-chain (scFvKT) anti-i diotypic antibodies were produced to represent the internal image of a yeas t killer toxin (KT) characterized by a wide spectrum of antimicrobial activ ity, including Gram-positive cocci. Pathogenic eukaryotic and prokaryotic m icroorganisms, such as Candida albicans, Pneumocystis carinii, and a multid rug-resistant strain of Mycobacterium tuberculosis, presenting specific, al though yet undefined, KT-cell wall receptors (KTR), have proven to be kille d in vitro by mAbKT and scFvKT, mAbKT and scFvKT exert a therapeutic effect in vivo in experimental models of candidiasis and pneumocystosis by mimick ing the functional activity of protective antibodies naturally produced in humans against KTR of infecting microorganisms. The swelling tide of concer n over increasing bacterial resistance to antibiotic drugs gives the impetu s to develop new therapeutic compounds against microbial threat. Thus, the in vitro bactericidal activity of mAbKT and scFvKT against gram-positive, d rug-resistant cocci of major epidemiologial interest was investigated. Materials and Methods: mAbKT and scFvKT generated by hybridoma and DNA reco mbinant technology from the spleen lymphocytes of mice immunized with a KT- neutralizing monoclonal antibody (mAb KT4) were used in a conventional colo ny 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. T hese bacterial strains are characterized by different patterns of resistanc e to antibiotics, including methicillin, vancomycin, and penicillin. Results: According to the: experimental conditions adopted, no bacterial is olate proved to be resistant to the activity of mAbKT and scFvKT. Conclusions: scFvKT exerted a microbicidal activity against multidrug resis tant bacteria, which may represent the basis for the drug modeling of new a ntibiotics with broad antibacterial spectra to tackle the emergence of micr obial resistance.