Department of Biomolecular Sciences and Biotechnology, Università degli Studi di Milano, Milan, Italy.
Appl Microbiol Biotechnol. 2010 Apr;86(3):813-23. doi: 10.1007/s00253-010-2468-8. Epub 2010 Feb 18.
Bacteria can switch between planktonic forms (single cells) and biofilms, i.e., bacterial communities growing on solid surfaces and embedded in a matrix of extracellular polymeric substance. Biofilm formation by pathogenic bacteria often results in lower susceptibility to antibiotic treatments and in the development of chronic infections; thus, biofilm formation can be considered an important virulence factor. In recent years, much attention has been directed towards understanding the biology of biofilms and towards searching for inhibitors of biofilm development and of biofilm-related cellular processes. In this report, we review selected examples of target-based screening for anti-biofilm agents: We focus on inhibitors of quorum sensing, possibly the most characterized target for molecules with anti-biofilm activity, and on compounds interfering with the metabolism of the signal molecule cyclic di-GMP metabolism and on inhibitors of DNA and nucleotide biosynthesis, which represent a novel and promising class of biofilm inhibitors. Finally, we discuss the activation of biofilm dispersal as a novel mode of action for anti-biofilm compounds.
细菌可以在浮游生物形式（单细胞）和生物膜之间转换，即细菌群落在固体表面生长并嵌入细胞外聚合物基质中。病原菌的生物膜形成通常会导致对抗生素治疗的敏感性降低，并导致慢性感染的发展；因此，生物膜形成可以被认为是一个重要的毒力因子。近年来，人们越来越关注理解生物膜的生物学特性，以及寻找抑制生物膜形成和与生物膜相关的细胞过程的抑制剂。在本报告中，我们回顾了基于靶标的抗生物膜剂筛选的一些例子：我们重点介绍群体感应抑制剂，这可能是具有抗生物膜活性的分子最具特征的靶标，以及干扰信号分子环二鸟苷酸代谢的化合物，以及干扰 DNA 和核苷酸生物合成的抑制剂，这代表了一类新型且有前途的生物膜抑制剂。最后，我们讨论了生物膜分散的激活作为抗生物膜化合物的一种新作用模式。
