Combating bacterial biofilms by combining systems biology and chemical biology tools

　　报告题目: Combating bacterial biofilms by combining systems biology and chemical biology tools

　　报告人:Yang Liang (杨亮)

　　报告人单位: Assistant Professor, School of Biological Sciences，Nanyang Technological University, Singapore

　　报告时间: 2015年4月15日(星期三)上午10:00点

　　报告地点: 微生物所A203会议室

　　主持人: 马旅雁研究员

　　报告摘要: A bacterial biofilm is a surface attached community of microorganisms embedded in and protected by an extracellular matrix of self-made biomolecules. The US National Institute of Health (NIH) has estimated that 65-80% of all microbial infections involve bacterial biofilms. Biofilm-based bacteria can evade the otherwise detrimental actions of immune responses and develop into chronic infections. Because the present day’s armory of conventional antimicrobials cannot efficiently eradicate biofilms, there is an urgent need to understand the fundamental mechanism of antibiotic resistance by biofilms. One major obstacle to study biofilm physiology is the heterogeneity in biofilms, which often confounds our efforts to target specific aspects of biofilm biology. Bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) is a global, intracellular secondary messenger that controls biofilm differentiation. High intracellular levels of c-di-GMP stimulate bacteria to form biofilms by enhancing synthesis of adhesive structures and biofilm matrix components while low intracellular levelsfaciliate motility and chemotaxis. The heterogeneity in biofilms often hinders the application of systems biology tools (e.g. transcriptomics and proteomics) in studying biofilm physiology. Here, we applied stable isotope labeling by amino acids in cell culture (SILAC) technology to selectively label the proteome from different subpopulations of biofilms. We found that type IV pili and quorum sensing (QS) are essential for the development of colistin-tolerant cells within P. aeruginosa biofilms. Applying dispersal agents that can reduce intracellular c-di-GMP content significantly reduces the development of colistin-tolerant cells in P. aeruginosa biofilms. However, the dispersed cells by either genetic approach or chemical approach have distinct physiology compared to biofilm cells and planktonic cells as their highly virulent phenotypes due to low expression level of two ncRNAs (RsmY and RsmZ) but high expression level of QS-regulated genes.