期刊
PLOS ONE
卷 14, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0215535
关键词
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资金
- Russian Science Foundation [14-50-00126, 14-23-00199, 16-14-00083]
- Russian Federal Agency of Scientific Organizations [0309-2017-0008]
- Franco-German ANR-DFG grant [ANR-16-CE92-0031-01 AFUINTERACT]
- Franco-Indian CEFIPRA grant [5403-1]
- Russian Science Foundation [16-14-00083] Funding Source: Russian Science Foundation
beta-(1 -> 3)-D-Glucan is an essential component of the fungal cell wall. Mouse monoclonal antibodies (mAbs) against synthetic nona- beta-(1 -> 3)-D-glucoside conjugated with bovine serum albumin (BSA) were generated using hybridoma technology. The affinity constants of two selected mAbs, 3G11 and 5H5, measured by a surface plasmon resonance biosensor assay using biotinylated nona- beta-(1 -> 3)-D-glucan as the ligand, were approximately 11 nM and 1.9 nM, respectively. The glycoarray, which included a series of synthetic oligosaccharide derivatives representing beta-glucans with different lengths of oligo-beta-(1 -> 3)-D-glucoside chains, demonstrated that linear tri-, penta- and nonaglucoside, as well as a beta-(1 -> 6)-branched octasaccharide, were recognized by mAb 5H5. By contrast, only linear oligo-beta-(1 -> 3)-D-glucoside chains that were not shorter than pentaglucosides (but not the branched octaglucoside) were ligands for mAb 3G11. Immunolabelling indicated that 3G11 and 5H5 interact with both yeasts and filamentous fungi, including species from Aspergillus, Candida, Penicillium genera and Saccharomyces cerevisiae, but not bacteria. Both mAbs could inhibit the germination of Aspergillus fumigatus conidia during the initial hours and demonstrated synergy with the antifungal fluconazole in killing C. albicans in vitro. In addition, mAbs 3G11 and 5H5 demonstrated protective activity in in vivo experiments, suggesting that these beta-glucan-specific mAbs could be useful in combinatorial antifungal therapy.
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