National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1281-6. doi: 10.1073/pnas.1115006109. Epub 2012 Jan 9.
Biofilms cause significant problems in the environment and during the treatment of infections. However, the molecular mechanisms underlying biofilm formation are poorly understood. There is a particular lack of knowledge about biofilm maturation processes, such as biofilm structuring and detachment, which are deemed crucial for the maintenance of biofilm viability and the dissemination of cells from a biofilm. Here, we identify the phenol-soluble modulin (PSM) surfactant peptides as key biofilm structuring factors in the premier biofilm-forming pathogen Staphylococcus aureus. We provide evidence that all known PSM classes participate in structuring and detachment processes. Specifically, absence of PSMs in isogenic S. aureus psm deletion mutants led to strongly impaired formation of biofilm channels, abolishment of the characteristic waves of biofilm detachment and regrowth, and loss of control of biofilm expansion. In contrast, induced expression of psm loci in preformed biofilms promoted those processes. Furthermore, PSMs facilitated dissemination from an infected catheter in a mouse model of biofilm-associated infection. Moreover, formation of the biofilm structure was linked to strongly variable, quorum sensing-controlled PSM expression in biofilm microenvironments, whereas overall PSM production remained constant to ascertain biofilm homeostasis. Our study describes a mechanism of biofilm structuring in molecular detail, and the general principle (i.e., quorum-sensing controlled expression of surfactants) seems to be conserved in several bacteria, despite the divergence of the respective biofilm-structuring surfactants. These findings provide a deeper understanding of biofilm development processes, which represents an important basis for strategies to interfere with biofilm formation in the environment and human disease.
生物膜在环境中和感染治疗过程中会引起严重问题。然而，生物膜形成的分子机制还了解甚少。对于生物膜成熟过程，例如生物膜结构和脱落，缺乏特别的了解，这些过程对于维持生物膜的存活和细胞从生物膜中的传播至关重要。在这里，我们确定了酚可溶性调节素 (PSM) 表面活性剂肽是主要生物膜形成病原体金黄色葡萄球菌的关键生物膜结构形成因子。我们提供的证据表明，所有已知的 PSM 类都参与了结构和脱落过程。具体来说，在同源性金黄色葡萄球菌 psm 缺失突变体中缺乏 PSM 会导致生物膜通道的形成严重受损，特征性生物膜脱落和再生长波的消失，以及对生物膜扩展的控制丧失。相比之下，在预先形成的生物膜中诱导表达 psm 基因座会促进这些过程。此外，PSM 促进了在生物膜相关感染的小鼠模型中从感染导管的传播。此外，生物膜结构的形成与生物膜微环境中强烈变化的群体感应控制的 PSM 表达有关，而整体 PSM 产生保持不变以确保生物膜平衡。我们的研究详细描述了生物膜结构形成的分子机制，并且该普遍原理（即群体感应控制表面活性剂的表达）似乎在几种细菌中是保守的，尽管各自的生物膜结构表面活性剂存在差异。这些发现为生物膜发育过程提供了更深入的了解，这是在环境和人类疾病中干扰生物膜形成的策略的重要基础。
