Alona Keren-Paz, Malena Cohen-Cymberknoh, Dror Kolodkin-Gal, Iris Karunker, Simon Dersch, Sharon G. Wolf, Tsviya Olender, Elena Kartvelishvily, Sergey Kapishnikov, Peninnah Green-Zelinger, Michal Shteinberg, Gideon Zamir, Assaf Gal, Peter Graumann, Eitan Kerem and Ilana Kolodkin-Gal

Bacterial biofilms produce a robust internal mineral layer, composed of calcite, which strengthens the colony and protects the residing bacteria from antibiotics. In this work, we provide evidence that the assembly of a functional mineralized macro-structure begins with mineral precipitation within a defined cellular compartment in a differentiated subpopulation of cells. Transcriptomic analysis of a model organism, Bacillus subtilis, revealed that calcium was essential for activation of the biofilm state, and highlighted the role of cellular metal homeostasis and carbon metabolism in biomineralization. The molecular mechanisms promoting calcite formation were conserved in pathogenic Pseudomonas aeruginosa biofilms, resulting in formation of calcite crystals tightly associated with bacterial cells in sputum samples collected from cystic fibrosis patients. Biomineralization inhibitors targeting calcium uptake and carbonate accumulation significantly reduced the damage inflicted by P. aeruginosa biofilms to lung tissues. Therefore, better understanding of the conserved molecular mechanisms promoting biofilm calcification can path the way to the development of novel classes of antibiotics to combat otherwise untreatable biofilm infections.

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