Fig. 1.

A frog antimicrobial peptide promotes the transepithelial passage of a cosecreted toxin. a Litoria caerulea (an Australian tree frog) attacked by the snake Dendrelaphis punctulatus. Note the defensive skin secretion (black arrow), known to contain toxins (including caerulein) and AMPs (photograph taken by Jannie Smit). b Amino-acid sequences of the X. laevis skin toxin caerulein (Cae) and its cosecreted antimicrobial peptide, caerulein precursor fragment (CPF). c Lactate dehydrogenase (LDH) leakage indicates cell damage in a Caco-2 epithelial model exposed to a mixture of caerulein and CPF but not to caerulein alone (n = 7; 100% corresponds to the LDH leakage caused by complete cell lysis as induced by Triton-X). d Co-administration of CPF induces a rapid prolonged drop in transepithelial electrical resistance (TEER) of Caco-2 monolayers (n = 9, one-way ANOVA, F(4, 40) = 1345.6, p < 0.0005). e Caerulein alone does not damage Caco-2 monolayers, but co-administration of CPF results in intercellular ruptures (white arrow), as revealed by scanning electron microscopy. Scale bars represent 100 μm. f Co-administration of CPF at the apical side leads to higher caerulein levels after 60 min at the basolateral side, indicating enhanced transepithelial transport across Caco-2 monolayers (n = 9, t-test, t(8.2) = −7.3, p < 0.0005) and an oral multilayer model (n = 8, t-tests, t(9.1) = −9.6, p < 0.0005). All data are mean ± s.e.m., error bars not shown when covered by data symbols