title: RIP-V improves murine survival in a sepsis model by down-regulating RNAIII expression and α-hemolysin release of methicillin-resistant Staphylococcus aureus.
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.
authors.forename: Bo
authors.initials: B
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Mingkai
authors.initials: M
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Yu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xue
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Da
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hou
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Luo
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use* / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects; D006460:Hemolysin Proteins / Q000378:metabolism*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000627:therapeutic use* / Q000633:toxicity; D012329:RNA, Bacterial / Q000096:biosynthesis* / Q000187:drug effects; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013534:Survival
chemical_list: D000900:Anti-Bacterial Agents; D006460:Hemolysin Proteins; D009842:Oligopeptides; D012329:RNA, Bacterial; C111711:RNAIII inhibiting peptide; C096035:RNAIII, Staphylococcus aureus