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A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia
Published on: September 21, 2019
RIP-V improves murine survival in a sepsis model by down-regulating RNAIII expression and α-hemolysin release of
Abstract:
Staphylococcus aureus is associated with serious invasive infections and high mortality rates due to a large number of toxins released. The persistent increasing resistance of S. aureus has driven the need for new anti-infection agents and innovative therapeutic strategies. RNAIII-inhibiting peptide (RIP) has been reported to reduce bacterial virulence by interfering with S. aureus quorum sensing system. The present study aimed to investigate whether two new RIP derivatives (RIP-V and RIP-L) could improve the survival rate of mice in a MRSA sepsis model. We found that neither anti-bacterial nor cell toxicity were displayed by all RIPs in vitro. In vivo protective effects were observed using a MRSA-induced mice sepsis model. Among RIPs, RIP-V exhibited the strongest protection function on mice survival and inhibition of pathological damages. Our studies firstly verified that RIPs could inhibited the RNAIII expression of S. aurues isolated from liver tissue of BALB/c mice. Moreover, RIP-V exhibited the strongest inhibitory effect on RNAIII and can decrease markedly the secretion of o-hemolysin in liver. These findings indicate that RIP-V might be considered as a potential and specific drug candidate for treating S. aureus infections, especially for MRSA.
Insights
New RNAIII-inhibiting peptides (RIPs) show promise against Staphylococcus aureus infections. RIP-V significantly improved survival rates in a mouse sepsis model by inhibiting bacterial RNAIII expression and toxin secretion.
Area of Science:
- Microbiology and Infectious Diseases
- Pharmacology and Drug Discovery
- Molecular Biology
Background:
- Staphylococcus aureus infections pose significant mortality risks due to potent toxins and increasing antibiotic resistance.
- Novel therapeutic strategies are crucial to combat persistent and drug-resistant S. aureus strains.
- RNAIII-inhibiting peptide (RIP) is a known virulence inhibitor targeting the S. aureus quorum sensing system.
Purpose of the Study:
- To evaluate the efficacy of two novel RNAIII-inhibiting peptide (RIP) derivatives, RIP-V and RIP-L, in a mouse model of MRSA sepsis.
- To assess the in vitro antibacterial activity and cytotoxicity of RIPs.
- To investigate the in vivo protective effects and mechanism of action of RIPs against S. aureus infection.
Main Methods:
- In vitro assessment of antibacterial activity and cytotoxicity of RIPs against S. aureus.
- Establishment of a MRSA-induced sepsis model in BALB/c mice to evaluate in vivo survival rates.
- Quantification of RNAIII expression and alpha-hemolysin secretion in liver tissues of infected mice.
Main Results:
- RIPs demonstrated no significant antibacterial activity or cytotoxicity in vitro.
- In vivo studies showed RIP-V significantly enhanced mouse survival and reduced pathological damage in a MRSA sepsis model.
- RIP-V effectively inhibited S. aureus RNAIII expression and decreased alpha-hemolysin secretion in liver tissues.
Conclusions:
- RIPs, particularly RIP-V, offer a potential therapeutic strategy for S. aureus infections by targeting virulence factors.
- RIP-V demonstrates significant protective effects in a MRSA sepsis model, suggesting its potential as a specific drug candidate.
- The mechanism involves the inhibition of RNAIII expression and subsequent reduction in toxin secretion.
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