Department of Pharmacy, University "G. d'Annunzio" of Chieti - Pescara, Chieti, Italy.
Curr Top Med Chem. 2018;18(24):2068-2079. doi: 10.2174/1568026618666181022120711.
S. aureus under the biofilm mode of growth is often related to several nosocomial infections, more frequently associated with indwelling medical devices (catheters, prostheses, portacaths or heart valves). As a biofilm, the biopolymer matrix provides an excellent growth medium, increasing the tolerance to antibiotics and host immune system. To date, the antimicrobial therapy alone is not effective. A novel strategy to prevent biofilm formation is based on the interference with the bacterial cell-cell communication, a process known as quorum sensing (QS) and mediated by the RNA-III-activating peptide (RAP) and its target protein TRAP (Target of RAP). The RNAIII inhibiting peptide (RIP) is able to inhibit S. aureus pathogenesis by disrupting QS mechanism competing with RAP, thus inhibiting the phosphorylation of TRAP. This alteration leads to a reduced adhesion and to the inhibition of RNAIII synthesis, with the subsequent suppression of toxins synthesis. The present paper will provide an overview on the activity and potential applications of RIP as biofilm inhibiting compound, useful in the management of S. aureus biofilm infections. Moreover, medicinal chemistry strategies have been examined to better understand which modifications and/or structure alterations were able to produce new derivatives of this QS inhibitor with an improved antibiofilm activity.
金黄色葡萄球菌在生物膜生长模式下常与几种医院获得性感染有关，更常与留置的医疗设备（导管、假体、端口或心脏瓣膜）有关。作为生物膜，生物聚合物基质提供了极好的生长介质，增加了对抗生素和宿主免疫系统的耐受性。迄今为止，单独的抗菌治疗并不有效。一种预防生物膜形成的新策略是基于干扰细菌细胞间通讯，这一过程被称为群体感应（QS），由 RNA-III-激活肽（RAP）及其靶蛋白 TRAP（RAP 的目标）介导。RNAIII 抑制肽（RIP）能够通过与 RAP 竞争来破坏 QS 机制，从而抑制 TRAP 的磷酸化，从而抑制 S. aureus 发病机制。这种改变导致黏附减少，并抑制 RNAIII 的合成，随后抑制毒素的合成。本文将概述 RIP 作为生物膜抑制化合物的活性和潜在应用，有助于管理 S. aureus 生物膜感染。此外，还研究了药物化学策略，以更好地了解哪些修饰和/或结构改变能够产生这种 QS 抑制剂的新衍生物，从而提高抗生物膜活性。
