Hemoglobin digestion is an essential process for blood-feeding parasites. Using chemical tools, we deconvoluted the intracellular hemoglobinolytic cascade in the tick Ixodes ricinus, a vector of Lyme disease and tick-borne encephalitis. In tick gut tissue, a network of peptidases was demonstrated through imaging with specific activity-based probes and activity profiling with peptidic substrates and inhibitors. This peptidase network is induced upon blood feeding and degrades hemoglobin at acidic pH. Selective inhibitors were applied to dissect the roles of the individual peptidases and to determine the peptidase-specific cleavage map of the hemoglobin molecule. The degradation pathway is initiated by endopeptidases of aspartic and cysteine class (cathepsin D supported by cathepsin L and legumain) and is continued by cysteine amino- and carboxy-dipeptidases (cathepsins C and B). The identified enzymes are potential targets to developing novel anti-tick vaccines.

• MeSH
• Cysteine Endopeptidases metabolism   MeSH
• Endopeptidases metabolism   MeSH
• Hemoglobins chemistry   metabolism   MeSH
• Enzyme Inhibitors pharmacology   MeSH
• Catalytic Domain MeSH
• Cathepsin B metabolism   MeSH
• Cathepsin C metabolism   MeSH
• Cathepsin D metabolism   MeSH
• Cathepsin L metabolism   MeSH
• Ixodes enzymology   MeSH
• Hydrogen-Ion Concentration MeSH
• Molecular Sequence Data MeSH
• Proteomics methods   MeSH
• Amino Acid Sequence MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• asparaginylendopeptidase MeSH Browser
• Cysteine Endopeptidases MeSH
• Endopeptidases MeSH
• Hemoglobins MeSH
• Enzyme Inhibitors MeSH
• Cathepsin B MeSH
• Cathepsin C MeSH
• Cathepsin D MeSH
• Cathepsin L MeSH