Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China; Laboratory for Functional Metabolomics Science, Shanghai Jiao Tong University, Shanghai, 200240, China.
Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China; Laboratory for Functional Metabolomics Science, Shanghai Jiao Tong University, Shanghai, 200240, China.
Anal Chim Acta. 2021 Feb 8;1145:26-36. doi: 10.1016/j.aca.2020.12.021. Epub 2020 Dec 17.
Biofilms are broadly formed by diverse microorganisms under stressful environments that are basically surrounded by an EPS matrix, which enable bacterial cells to confer the resistance to the biocides, antibiotics and other invasions. Yet, biofilms cause harmful impacts in various fields, including clinical infections, food contaminations and environmental pollution. However, the mechanism of biofilm formation remains incompletely elucidated, and currently, we lack an efficient strategy to tackle these tough problems by eradicating biofilms. In the present study, we sought to decipher the mechanism of biofilm formation in Escherichia coli from metabolic perspective. By exposing bacterial cells to various concentrations of iron, we found that iron can regulate biofilm formation, and the phenotypic changes were obviously dependent on iron concentration. A functional metabolome assay was further implemented to investigate the regulatory mechanism of iron on biofilm formation; we verified that siderophores mostly account for the transportation of iron into bacterial cells. Then, the bioavailable iron was recruited by bacterial cells to direct the levels of five functional metabolites (l-tryptophan, 5'-MTA, spermidine, CMP and L-leucine), which were identified as new effectors that directly regulate biofilm formation. Taken together, this study is the first to identify five functional metabolites to efficiently regulate biofilm formation, which can be targeted to tackle the harmful impacts associated with biofilm formation in different niches.
生物膜是在应激环境下由多种微生物广泛形成的，其基本结构被 EPS 基质所包围，使细菌细胞能够赋予其对杀菌剂、抗生素和其他入侵物的抗性。然而，生物膜在多个领域造成了有害影响，包括临床感染、食品污染和环境污染。然而，生物膜形成的机制仍不完全清楚，目前我们缺乏有效的策略来通过消除生物膜来解决这些难题。在本研究中，我们从代谢角度试图揭示大肠杆菌生物膜形成的机制。通过将细菌细胞暴露于不同浓度的铁中，我们发现铁可以调节生物膜的形成，表型变化明显依赖于铁浓度。进一步实施功能代谢组学测定来研究铁对生物膜形成的调节机制；我们验证了铁载体主要负责将铁运输到细菌细胞中。然后，细菌细胞招募可利用的铁来直接调节五个功能代谢物（l-色氨酸、5'-MTA、腐胺、CMP 和 L-亮氨酸）的水平，这些代谢物被鉴定为直接调节生物膜形成的新效应物。总之，这项研究首次鉴定了五个功能代谢物来有效地调节生物膜的形成，这可以作为针对不同生态位中与生物膜形成相关的有害影响的靶点。
