Inhibition of beta-1,3-glucan synthase and cell growth of Cryptococcus species by recombinant single-chain anti-idiotypic antibodies.
Recombinant single-chain fragment variable (scFv) anti-idiotypic antibodies were produced to represent the internal image of a HM-1 killer toxin, which is characterized by a wide spectrum of anti-fungal activity through inhibiting beta-1,3-glucan synthase (GS). We examined if scFv antibodies are active against Cryptococcus species, a human pathogen of increasing medical importance. The anti-cryptococcal activity of scFv antibodies and HM-1 were assessed by MIC analysis for C. neoformans IFM 40215 and C. albidus NBRC 0612 cells. The scFv antibodies had strong anti-cryptococcal activity in vitro with IC50 at 1.07 x 10(-7) to 2.60 x 10(-7) M for C. neoformans and C. albidus. Furthermore, the scFv antibodies potentially inhibited GS of C. neoformans with IC50 at 1.27 x 10(-7) to 2.27 x 10(-7) M. Both the anti-fungal and anti-GS activities of the scFv antibodies were markedly neutralized by the monoclonal antibody that neutralizes HM-1 killer toxin.
Selvakumar
Dakshnamurthy
D
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 5-13-2 Kamishinei-cho, Niigata 950-2081, Japan.
Miyamoto
Masahiko
M
Furuichi
Yasuhiro
Y
Komiyama
Tadazumi
T
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D003454:Cryptococcus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors; D007128:Immunoglobulin Fragments / Q000494:pharmacology*; D055646:Killer Factors, Yeast; D008826:Microbial Sensitivity Tests; D009183:Mycotoxins / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D000935:Antifungal Agents; D007128:Immunoglobulin Fragments; D055646:Killer Factors, Yeast; D009183:Mycotoxins; D011994:Recombinant Proteins; C055966:immunoglobulin Fv; D005964:Glucosyltransferases; C020570:1,3-beta-glucan synthase