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Daptomycin is an important antibiotic for the treatment of infections caused by  Staphylococcus aureus . The emergence of daptomycin resistance in  S. aureus  is associated with treatment failure and persistent infections with poor clinical outcomes. Here, we investigated host innate immune responses against clinically derived, daptomycin-resistant (DAP-R) and -susceptible  S. aureus  paired isolates using a zebrafish infection model. We showed that the control of DAP-R  S. aureus  infections was attenuated in vivo due to cross-resistance to host cationic antimicrobial peptides. These data provide mechanistic understanding into persistent infections caused by DAP-R  S. aureus  and provide crucial insights into the adaptive evolution of this troublesome pathogen.

The Resistance to Host Antimicrobial Peptides in Infections Caused by Daptomycin-Resistant Staphylococcus aureus