Antibody fragment based antifungal conjugate selectively targeting candida

An antibody fragment based antifungal conjugate selectively targeting Candida spp., comprising

• an antimicrobial peptide at one end of the conjugate,
• an antibody fragment at the other end of the conjugate that is a camelid heavy chain antibody variable region fragment (VHH) specific against an antigen of Candida spp. selected from the group consisting of surface antigen, and extracellular matrix antigen of Candida biofilm,
• at least one signal protease cleavage sequence susceptible to cleavage by proteases selected from the group consisting of membrane proteases, cell wall associated proteases, secreted proteases of Candida spp., and proteases of host neutrophils;
• and at least one flexible polypeptide linker in tandem with the signal protease cleavage sequence, with the signal protease cleavage sequence and the polypeptide linker placed in between the antimicrobial peptide and antibody fragment;
• wherein,
• the amino acid sequence of the conjugate is SEQ ID NO:
• 19 consisting of antimicrobial peptide of SEQ ID NO:
• 2, a protease specific cleavage sequence of SEQ ID NO:
• 10 which is susceptible to cleavage by virulent protease secreted aspartyl proteinase-1 (SAP1) secreted by Candida spp., a flexible Glycine Serine linker of SEQ ID NO:
• 14, and antibody fragment of SEQ ID NO:
• 9 targeting Candida spp. specific enolase which is a virulence factor protease and biofilm specific antigen of Candida spp.;
• and
• the in vitro MIC-99 of the conjugate of SEQ ID NO:
• 19 against Candida albicans is 0.25 μm.