The requirement for the native HNP1 fold for microbicidal activity is consistent with a previous report demonstrating that an all Cys-to-Ala analog of HNP1 was nearly 10-fold less potent in bactericidal assays than the native peptide [38] . Similarly, disruption of disulfide linkages by mutagenesis of Cys residues to Ala or Ser in the human Paneth cell a-defensin HD5 reduced in vitro bactericidal activity demonstrating the requirement for the disulfides for in vitro bactericidal activity of this peptide [39] . In contrast, disruption of disulfide linkages in mouse enteric defensin, Crp4, by Cys-to-Ala mutagenesis did not eliminate microbicidal activities of the peptide [40] .