Antimicrobial peptide-antibiotic synergy exerts anti-streptococcus suis infection by membrane disruption, ROS

Yandi Pan1, Hongdou Liu1, Yuqian Liu1

  • 1Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing 400715, China.

Insights

Chicken antimicrobial peptide CATH-1 combined with tetracycline effectively combats multidrug-resistant Streptococcus suis. This synergy enhances survival, reduces bacterial load, and inhibits resistance development.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Drug Discovery

Background:

  • Multidrug-resistant Streptococcus suis (S. suis) poses a significant global health threat.
  • Antimicrobial peptides (AMPs) combined with antibiotics offer a strategy to enhance efficacy and overcome resistance.

Purpose of the Study:

  • To investigate the synergistic antibacterial efficacy of chicken-derived AMP CATH-1 and tetracycline against S. suis.
  • To evaluate the in vitro and in vivo effectiveness of this combination therapy.

Main Methods:

  • In vitro antibacterial assays demonstrating rapid killing of S. suis.
  • In vivo mouse infection model to assess survival rates, bacterial load, and inflammatory responses.
  • Mechanistic studies including SEM, SYTO9/PI staining, ROS and PMF assays, efflux pump inhibition, and biofilm formation analysis.

Main Results:

  • The CATH-1 and tetracycline combination rapidly killed S. suis in vitro.
  • In vivo, the combination therapy improved survival, reduced bacterial burden, and mitigated inflammation and tissue damage.
  • CATH-1 demonstrated membrane disruption, increased ROS and PMF disruption, inhibited efflux pumps, and reduced biofilm formation, thereby lowering tetracycline resistance emergence.

Conclusions:

  • CATH-1 and tetracycline exhibit significant synergistic activity against S. suis infection.
  • This combination therapy provides a promising approach for treating S. suis infections and combating antimicrobial resistance.
  • AMPs like CATH-1 can be developed as effective additives to conventional antibiotics.

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