TY - UNPB
T1 - The formation of microbial exoskeletons is driven by a controlled calcium-concentrating subcellular niche
AU - Keren-Paz, Alona
AU - Cohen-Cymberknoh, Malena
AU - Kolodkin-Gal, Dror
AU - Peretz, Shani
AU - Karunker, Iris
AU - Wolf, Sharon G.
AU - Olender, Tsviya
AU - Kapishnikov, Sergey
AU - Brumfield, Vlad
AU - Dersch, Simon
AU - Kartvelishvily, Elena
AU - Green-Zelinger, Peninnah
AU - Isola-Adeyanju, Damilola
AU - Suissa, Ronit
AU - Shteinberg, Michal
AU - McLeod, Daniel
AU - Patrauchan, Marianna
AU - Zamir, Gideon
AU - Gal, Assaf
AU - Graumann, Peter L.
AU - Kerem, Eitan
AU - Kolodkin-Gal, Ilana
PY - 2021/1/1
Y1 - 2021/1/1
N2 - In nature, bacteria reside in biofilms - multicellular differentiated communities held together by extracellular matrix. In this work, we identified a novel subpopulation essential for biofilm formation – mineral-forming cells. This subpopulation contains an intracellular calcium-accumulating niche, in which the formation of a calcium carbonate mineral is initiated. As the biofilm colony develops, this mineral grows in a controlled manner, forming a functional macrostructure that serves the entire community.The molecular mechanisms promoting calcite scaffold formation were conserved between three distant phyla – the Gram-positive Bacillus subtilis, Gram-negative Pseudomonas aeruginosa and the actinobacterium Mycobacterium abscessus. Biofilm development of all three species was similarly impaired by inhibition of calcium uptake and carbonate accumulation. Moreover, chemical inhibition and mutations targeting mineralization both significantly reduced the attachment of P. aeruginosa to the lung, as well as the subsequent damage inflicted by biofilms to lung tissues, and restored their sensitivity to antibiotics.The evolutionary conserved cellular pathway controlling the fundamental feature of biofilm development uncovered in this work offers novel druggable targets for antibiotics to combat otherwise untreatable biofilm infections.Competing Interest StatementThe authors have declared no competing interest.
AB - In nature, bacteria reside in biofilms - multicellular differentiated communities held together by extracellular matrix. In this work, we identified a novel subpopulation essential for biofilm formation – mineral-forming cells. This subpopulation contains an intracellular calcium-accumulating niche, in which the formation of a calcium carbonate mineral is initiated. As the biofilm colony develops, this mineral grows in a controlled manner, forming a functional macrostructure that serves the entire community.The molecular mechanisms promoting calcite scaffold formation were conserved between three distant phyla – the Gram-positive Bacillus subtilis, Gram-negative Pseudomonas aeruginosa and the actinobacterium Mycobacterium abscessus. Biofilm development of all three species was similarly impaired by inhibition of calcium uptake and carbonate accumulation. Moreover, chemical inhibition and mutations targeting mineralization both significantly reduced the attachment of P. aeruginosa to the lung, as well as the subsequent damage inflicted by biofilms to lung tissues, and restored their sensitivity to antibiotics.The evolutionary conserved cellular pathway controlling the fundamental feature of biofilm development uncovered in this work offers novel druggable targets for antibiotics to combat otherwise untreatable biofilm infections.Competing Interest StatementThe authors have declared no competing interest.
U2 - 10.1101/2020.01.08.898569
DO - 10.1101/2020.01.08.898569
M3 - Preprint
T3 - bioRxiv
SP - 2020.01.08.898569
BT - The formation of microbial exoskeletons is driven by a controlled calcium-concentrating subcellular niche
ER -