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

Md Saruar Bhuiyan,Jhih-Hang Jiang,Xenia Kostoulias,Ravali Theegala,Graham J Lieschke,Anton Y Peleg

doi:10.3390/antibiotics10020096

Md Saruar Bhuiyan, Jhih-Hang Jiang + Show 4 more

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https://doi.org/10.3390/antibiotics10020096

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Abstract

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.

Highlights

Staphylococcus aureus continues to be one of the most important human bacterial pathogens, with the capacity to cause a broad range of infections, including S. aureus bacteremia (SAB) [1,2,3]
We collected S. aureus isolates from a patient with a complicated and persistent bloodstream infection that was treated with daptomycin but failed therapy, including a DAP-S parental strain, A8819, and its corresponding DAP-R daughter strain, A8817, that emerged after clinical failure [9]
To investigate the relationship between daptomycin resistance and persistent infections, we first measured the capacity of human whole blood to kill the paired DAP-S and DAP-R isolates ex vivo

Summary

Introduction

Staphylococcus aureus continues to be one of the most important human bacterial pathogens, with the capacity to cause a broad range of infections, including S. aureus bacteremia (SAB) [1,2,3]. Treatments of SAB caused by methicillin-resistant S. aureus (MRSA) have increasingly relied on last-line antibiotics, vancomycin and daptomycin [4,5,6]. The mechanisms of daptomycin actions are proposed to be similar to host cationic antimicrobial peptides (CAMPs) [7,8]. The emergence of daptomycin resistance has been associated with persistent and complicated staphylococcal infections in patients [4,9]. Recent studies have shown that clinically derived daptomycin-resistant (DAP-R) isolates caused persistent infections in Galleria mellonella infections and murine septicemia models [10,11,12,13]. The correlation between daptomycin resistance and prolonged bacterial survival in the infected host demands further investigation

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