Gov Y, Bitler A, Dell'Acqua G, Torres J V, Balaban N
Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Peptides. 2001 Oct;22(10):1609-20. doi: 10.1016/s0196-9781(01)00496-x.
Staphylococcus aureus are gram-positive bacteria that can cause serious diseases in humans and animals. S. aureus infections can be prevented by the heptapeptide RNAIII inhibiting peptide (RIP). RIP was originally isolated from culture supernatants of coagulase negative staphylococci presumed to be S. xylosus. The sequence of RIP was identified as YSPXTNF. Native RIP and its synthetic analogue YSPWTNF have been shown to be effective inhibitors of diseases caused by various strains of S. aureus, including, cellulitis, keratitis, septic arthritis, osteomylitis and mastitis. RIP is therefore considered to be a global inhibitor of S. aureus. We show here that: 1) the amide form of RIP (YSPWTNF-NH2) is highly stable and is therefore the one recommended for use. 2) RIP inhibits S. aureus pathogenesis by inhibiting the synthesis of both agr transcripts RNAII and RNAIII. 3) Although RIP inhibits agr, it also reduces bacterial adherence to mammalian cells and to plastic (tested on HEp2 cells and on polystyrene by fluorescence and atomic force microscopy), suggesting that RIP can be used safely as a therapeutic molecule. 4) RIP derivatives were designed and tested for their ability to inhibit RNAIII in vitro and cellulitis in vivo. Not all peptides that inhibited RNAIII also inhibited an infection in vivo, indicating that studies must be carried out in vivo before considering a peptide to be of therapeutic potential. 5) The RIP derivative containing Lysine and Isoleucine at positions 2 and 4, respectively, inhibited S. aureus infections in vivo (tested on cellulitis), suggesting that both RIP YSPWTNF and its derivative YKPITNF are effective inhibitors of infections caused by S. aureus.
金黄色葡萄球菌是革兰氏阳性菌，可在人类和动物中引发严重疾病。七肽RNAIII抑制肽（RIP）可预防金黄色葡萄球菌感染。RIP最初是从推测为木糖葡萄球菌的凝固酶阴性葡萄球菌的培养上清液中分离出来的。RIP的序列被鉴定为YSPXTNF。天然RIP及其合成类似物YSPWTNF已被证明是由各种金黄色葡萄球菌菌株引起的疾病的有效抑制剂，包括蜂窝织炎、角膜炎、化脓性关节炎、骨髓炎和乳腺炎。因此，RIP被认为是金黄色葡萄球菌的一种全面抑制剂。我们在此表明：1）RIP的酰胺形式（YSPWTNF-NH2）高度稳定，因此是推荐使用的形式。2）RIP通过抑制agr转录本RNAII和RNAIII的合成来抑制金黄色葡萄球菌的发病机制。3）尽管RIP抑制agr，但它也会降低细菌对哺乳动物细胞和塑料的粘附（通过荧光和原子力显微镜在HEp2细胞和聚苯乙烯上进行测试），这表明RIP可以安全地用作治疗分子。4）设计并测试了RIP衍生物在体外抑制RNAIII和在体内抑制蜂窝织炎的能力。并非所有抑制RNAIII的肽在体内也能抑制感染，这表明在认为一种肽具有治疗潜力之前必须进行体内研究。5）分别在第2位和第4位含有赖氨酸和异亮氨酸的RIP衍生物在体内抑制金黄色葡萄球菌感染（在蜂窝织炎上进行测试），这表明RIP YSPWTNF及其衍生物YKPITNF都是金黄色葡萄球菌引起的感染的有效抑制剂。
