Cohen-Cymberknoh Malena, Kolodkin-Gal Dror, Keren-Paz Alona, Peretz Shani, Brumfeld Vlad, Kapishnikov Sergey, Suissa Ronit, Shteinberg Michal, McLeod Daniel, Maan Harsh, Patrauchan Marianna, Zamir Gideon, Kerem Eitan, Kolodkin-Gal Ilana
Pediatric Pulmonary Unit and Cystic fibrosis Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel.
Department of Experimental Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
iScience. 2022 Apr 11;25(5):104234. doi: 10.1016/j.isci.2022.104234. eCollection 2022 May 20.
Biofilms are differentiated microbial communities held together by an extracellular matrix. μCT X-ray revealed structured mineralized areas within biofilms of lung pathogens belonging to two distant phyla - the proteobacteria and the actinobacteria . Furthermore, calcium chelation inhibited the assembly of complex bacterial structures for both organisms with little to no effect on cell growth. The molecular mechanisms promoting calcite scaffold formation were surprisingly conserved between the two pathogens as biofilm development was similarly impaired by genetic and biochemical inhibition of calcium uptake and carbonate accumulation. Moreover, chemical inhibition and mutations targeting mineralization significantly reduced the attachment of to the lung, as well as the subsequent damage inflicted by biofilms to lung tissues, and restored their sensitivity to antibiotics. This work offers underexplored druggable targets for antibiotics to combat otherwise untreatable biofilm infections.
生物膜是由细胞外基质维系在一起的分化微生物群落。μCT X射线显示，在属于两个不同门的肺部病原体生物膜内存在结构化矿化区域，这两个门分别是变形菌门和放线菌门。此外，钙螯合抑制了这两种生物体复杂细菌结构的组装，对细胞生长几乎没有影响。促进方解石支架形成的分子机制在这两种病原体之间惊人地保守，因为生物膜的发育同样会受到钙摄取和碳酸盐积累的基因和生化抑制的损害。此外，针对矿化的化学抑制和突变显著降低了病原体对肺部的附着，以及生物膜对肺组织造成的后续损伤，并恢复了它们对抗生素的敏感性。这项研究为抗生素提供了尚未充分探索的可成药靶点，以对抗原本无法治疗的生物膜感染。
