Abstract
Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans.
Highlights
ScFvs have been proved to be stable and can be produced rapidly, implying that they have the potential to be developed into therapeutics[19]
After 3 rounds of regular bio-panning with rSap[2], phages with strong affinities and slow off-rates were obtained. 70 clones were sequenced, 43 and 27 full-length scFvs clones were found in library J and I, respectively
This study presents a potential new strategy in systemic candidiasis therapy
Summary
ScFvs have been proved to be stable and can be produced rapidly, implying that they have the potential to be developed into therapeutics[19]. The secreted aspartyl proteinases (Saps) of C. albicans are encoded by a family of 10 SAP genes[20] and have been considered as key virulence determinants of C. albicans. They are clustered into three distinct groups, each of which are characterized by close sequence homology and physiological relevance[21]. The survival percentage of scFv-phage-treated Candida-infected animals was increased. These novel therapeutic materials combine the advantages of bacteriophage and single chain variable fragments, to provide a potential candidate for the therapy of systemic infection caused by C. albicans
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