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 epidemiological 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.
Subject(s)
Antibodies, Monoclonal/pharmacology , Fungal Proteins/immunology , Gram-Positive Cocci/drug effects , Mycotoxins/immunology , Yeasts/metabolism , Animals , Anti-Bacterial Agents/pharmacology , Antibodies, Monoclonal/immunology , Drug Resistance, Microbial , Fungal Proteins/pharmacology , Killer Factors, Yeast , Mice , Molecular Mimicry , Mycotoxins/pharmacology , Rats , Yeasts/immunologyABSTRACT
A strategy for the prevention and control of candidiasis, pneumocystosis, and tuberculosis, based on the idiotypic network of the yeast killer effect has been envisaged. Anti-idiotypic antibodies representing the internal image of a candidacidal, pneumocysticidal, and mycobactericidal killer toxin from Pichia anomala and idiotypes of killer toxin-neutralizing monoclonal antibodies mimicking the specific cell wall receptor of sensitive microorganisms might provide a unique approach for engineering innovative antibiotics and vaccines active against taxonomically unrelated pathogenic microorganisms. The rationale of the strategy relies on a phenomenon of microbial competition which has been mutated by the immune system in the response to natural infections.
Subject(s)
Infection Control , Mycotoxins/therapeutic use , Pichia , Animals , Cloning, Molecular , Drug Carriers , Humans , Killer Factors, Yeast , Lactobacillus , Mycobacterium/genetics , Mycotoxins/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/therapeutic use , TransgenesSubject(s)
Antibodies, Anti-Idiotypic/immunology , Antibodies, Fungal/immunology , Fungi/immunology , Mycoses/immunology , Mycotoxins/immunology , Animals , Antibodies, Anti-Idiotypic/therapeutic use , Antibodies, Monoclonal , Fungal Proteins , Fungi/metabolism , Humans , Killer Factors, Yeast , Mycoses/prevention & control , Mycoses/therapy , Mycotoxins/metabolismABSTRACT
Between 1987 and 1994, the prevalence of antibodies to Cytomegalovirus (CMV) was determined by ELISA in 19,043 subjects in the population of Parma (Northern Italy). The overall prevalence was 71.8%. The age specific prevalence increases starting from 28% in two year-olds to 95.7% in 45-54 year-old subjects. Profiles of antibody production during primary and recurrent infection were analyzed and correlated with virus presence in clinical samples showing correspondence between virus excretion and increasing IgG levels. A longitudinal study of CMV infection was undertaken in 1045 pregnant women and their babies. Rate of infection during pregnancy was 2.34% and rate of congenital infection was 0.57%. Results also indicate that mothers are the major source of perinatal infection (contaminated genital secretions and milk) and confirm the usefulness of monitoring antibody status and virus excretion of mother and neonate at birth.
