title: Proteomic analysis of human skin treated with larval schistosome peptidases reveals distinct invasion strategies among species of blood flukes.
abstract: BACKGROUND
  Skin invasion is the initial step in infection of the human host by schistosome blood flukes. Schistosome larvae have the remarkable ability to overcome the physical and biochemical barriers present in skin in the absence of any mechanical trauma. While a serine peptidase with activity against insoluble elastin appears to be essential for this process in one species of schistosomes, Schistosoma mansoni, it is unknown whether other schistosome species use the same peptidase to facilitate entry into their hosts.
  
  
  METHODS
  Recent genome sequencing projects, together with a number of biochemical studies, identified alternative peptidases that Schistosoma japonicum or Trichobilharzia regenti could use to facilitate migration through skin. In this study, we used comparative proteomic analysis of human skin treated with purified cercarial elastase, the known invasive peptidase of S. mansoni, or S. mansoni cathespin B2, a close homolog of the putative invasive peptidase of S. japonicum, to identify substrates of either peptidase. Select skin proteins were then confirmed as substrates by in vitro digestion assays.
  
  
  CONCLUSIONS
  This study demonstrates that an S. mansoni ortholog of the candidate invasive peptidase of S. japonicum and T. regenti, cathepsin B2, is capable of efficiently cleaving many of the same host skin substrates as the invasive serine peptidase of S. mansoni, cercarial elastase. At the same time, identification of unique substrates and the broader species specificity of cathepsin B2 suggest that the cercarial elastase gene family amplified as an adaptation of schistosomes to human hosts.
authors: Tetrad Graduate Program, University of California San Francisco, San Francisco, California, USA.
authors: Jessica
authors: J
authors: Ingram
authors: Giselle
authors: G
authors: Knudsen
authors: K C
authors: KC
authors: Lim
authors: Elizabeth
authors: E
authors: Hansell
authors: Judy
authors: J
authors: Sakanari
authors: James
authors: J
authors: McKerrow
mesh_terms: D000818:Animals; D006801:Humans; D007814:Larva / Q000201:enzymology / Q000472:pathogenicity; D010447:Peptide Hydrolases / Q000378:metabolism*; D059748:Proteolysis; D020543:Proteome / Q000032:analysis*; D012549:Schistosoma japonicum / Q000201:enzymology / Q000472:pathogenicity; D012550:Schistosoma mansoni / Q000201:enzymology* / Q000472:pathogenicity; D012867:Skin / Q000737:chemistry* / Q000469:parasitology*
chemical_list: D020543:Proteome; D010447:Peptide Hydrolases