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Intracranial Subarachnoidal Route of Infection for Investigating Roles of Streptococcus suis Biofilms in Meningitis in a Mouse Infection Model
Published on: July 1, 2018
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.
Abstract:
With the increasing emergence of antimicrobial resistance, the rise of multidrug-resistant Streptococcus suis (S. suis) has caused a great threat on global public health. The combination of antimicrobial peptide (AMP) and antibiotics is an efficient strategy to enhance antibacterial efficacy and combat bacterial antibiotic resistance. In this study, the antibacterial efficacy of chicken-derived AMP CATH-1 combined with tetracycline against S. suis infection was investigated in vitro and in vivo. The results showed that combination of CATH-1 and tetracycline exerted effectively anti-S. suis activity, which rapidly killed all tested bacteria in 60 min. In the mice infection model, CATH-1 combined with tetracycline improved survival rate of SC19-infected mice, reduced bacterial load in different tissues and alleviated the inflammatory response as well as inflammatory damage. Furthermore, CATH-1 reduced the emergence of bacterial resistance to tetracycline. Mechanically, CATH-1 disrupted cell membrane via SEM observation and SYTO9/PI staining. CATH-1 in combination with tetracycline aggravated reactive oxygen species (ROS) accumulation and proton motive force (PMF) disruption compared to CATH-1 or tetracycline alone. In addition, CATH-1 inhibited efflux pump function. Importantly, we identified a critical gene steAB associated with biofilm formation and CATH-1 alone or in combination with tetracycline inhibited biofilm formation. Our study shows effective anti-S. suis infection of CATH-1-tetracycline synergy, which provides the basis on the development of AMP as additives to antibiotics.
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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