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

Md Saruar Bhuiyan1, Jhih-Hang Jiang1, Xenia Kostoulias1

  • 1Infection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, VIC 3800, Australia.

Antibiotics (Basel, Switzerland)
|January 27, 2021
PubMed

Insights

Daptomycin-resistant Staphylococcus aureus infections are hard to control because they resist the body's own germ-killing peptides. This resistance leads to persistent infections and treatment failure.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Immunology

Background:

  • Daptomycin is a critical antibiotic for treating Staphylococcus aureus infections.
  • Emergence of daptomycin resistance (DAP-R) in S. aureus leads to treatment failure and persistent infections.
  • Understanding host-pathogen interactions is crucial for combating resistant bacteria.

Purpose of the Study:

  • To investigate host innate immune responses against daptomycin-resistant (DAP-R) and daptomycin-susceptible S. aureus.
  • To elucidate the mechanisms underlying the persistence of DAP-R S. aureus infections.
  • To explore the adaptive evolution of S. aureus in response to daptomycin and host immunity.

Main Methods:

  • Utilized a zebrafish infection model to compare host responses to DAP-R and DAP-susceptible S. aureus.
  • Analyzed bacterial survival and host immune cell recruitment in vivo.
  • Assessed the susceptibility of DAP-R and DAP-susceptible strains to host cationic antimicrobial peptides.

Main Results:

  • Host innate immune response control was attenuated against DAP-R S. aureus in the zebrafish model.
  • DAP-R S. aureus exhibited cross-resistance to host cationic antimicrobial peptides, hindering immune clearance.
  • Differences in immune evasion strategies were observed between DAP-R and DAP-susceptible isolates.

Conclusions:

  • Cross-resistance to host antimicrobial peptides contributes to the persistence of DAP-R S. aureus infections.
  • Mechanistic understanding of DAP-R S. aureus pathogenesis is enhanced by this study.
  • Findings provide insights into the adaptive evolution of S. aureus and potential therapeutic strategies.
Keywords:
S. aureusantimicrobial peptidesdaptomycinpersistent infection

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