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Calcium carbonate mineralization is essential for biofilm formation and lung colonization.
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.
Afiliación
  • Cohen-Cymberknoh M; Pediatric Pulmonary Unit and Cystic fibrosis Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel.
  • Kolodkin-Gal D; Department of Experimental Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • Keren-Paz A; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
  • Peretz S; National Center for Antibiotic Resistance and Infection Control, Tel Aviv Medical Center, Tel Aviv, Israel.
  • Brumfeld V; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
  • Kapishnikov S; Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel.
  • Suissa R; Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel.
  • Shteinberg M; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
  • McLeod D; Pulmonology Institute and CF Center, Carmel Medical Center, Haifa, Israel.
  • Maan H; Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, OK, USA.
  • Patrauchan M; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
  • Zamir G; Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, OK, USA.
  • Kerem E; Department of Experimental Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • Kolodkin-Gal I; Pediatric Pulmonary Unit and Cystic fibrosis Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel.
iScience ; 25(5): 104234, 2022 May 20.
Article en En | MEDLINE | ID: mdl-35521519
ABSTRACT
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.
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Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2022 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2022 Tipo del documento: Article