Calcium carbonate mineralization is essential for biofilm formation and lung colonization
Malena Cohen-Cymberknoh,
Dror Kolodkin-Gal,
Alona Keren-Paz,
Shani Peretz,
Vlad Brumfeld,
Sergey Kapishnikov,
Ronit Suissa,
Michal Shteinberg,
Daniel McLeod,
Harsh Maan,
Marianna Patrauchan,
Gideon Zamir,
Eitan Kerem,
Ilana Kolodkin-Gal
Affiliations
Malena Cohen-Cymberknoh
Pediatric Pulmonary Unit and Cystic fibrosis Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel
Dror Kolodkin-Gal
Department of Experimental Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Alona Keren-Paz
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel; National Center for Antibiotic Resistance and Infection Control, Tel Aviv Medical Center, Tel Aviv, Israel
Shani Peretz
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Vlad Brumfeld
Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel
Sergey Kapishnikov
Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel
Ronit Suissa
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Michal Shteinberg
Pulmonology Institute and CF Center, Carmel Medical Center, Haifa, Israel
Daniel McLeod
Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, OK, USA
Harsh Maan
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
Marianna Patrauchan
Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, OK, USA
Gideon Zamir
Department of Experimental Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Eitan Kerem
Pediatric Pulmonary Unit and Cystic fibrosis Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel; Corresponding author
Ilana Kolodkin-Gal
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel; Corresponding author
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 Pseudomonas aeruginosa and the actinobacteria Mycobacterium abscessus. 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 P. aeruginosa 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.
