Impact of daptomycin resistance on in vivo virulence and host immune responses. (A) Survival of the clinical DAP-R isolate A8817 and its parental DAP-S strain A8819 over 3 h in human blood (n = 4; * p < 0.05, Mann–Whitney test). (B) Survival of zebrafish following bloodstream infection with live S. aureus isolates (n = 30 embryos, three biological replicates; P value is a comparison of A8819 and A8817 by log-rank test). (C) Survival of the clinical DAP-R isolate A8817 and its parental DAP-S strain A8819 over 2 h in the presence of 20 μg/mL and 40 μg/mL hNP-1 (n = 3; for A8817 versus A8819, * p < 0.05 and ** p < 0.01 at indicated time points for same dosages, Student’s t-tests). Error bars represent the mean ± SEM. hNP-1: human neutrophil peptide 1.

Impact of daptomycin resistance on infection control by antimicrobial peptides in vivo. Survival of zebrafish infected with (A) A8819 and (B) A8817 after treatments with dorsomorphin or dimethyl sulfoxide (DMSO, solvent for dorsomorphin). (C) Survival of zebrafish infected with A8819 and A8817 after injections with hepcidin morpholino oligos (MO) or scrambled morpholino oligos (control). (n = 25 embryos, three biological replicates; p value is a comparison of dorsomorphin and DMSO for (A), hepcidin morpholino and the negative control for A8819 for (C) by log-rank test).