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The anti-cancerous drug doxorubicin decreases the c-di-GMP content in Pseudomonas aeruginosa but promotes biofilm formation.
Groizeleau, Julie; Rybtke, Morten; Andersen, Jens Bo; Berthelsen, Jens; Liu, Yang; Yang, Liang; Nielsen, Thomas E; Kaever, Volkhard; Givskov, Michael; Tolker-Nielsen, Tim.
Afiliação
  • Groizeleau J; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Rybtke M; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Andersen JB; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Berthelsen J; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Liu Y; Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore.
  • Yang L; Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore.
  • Nielsen TE; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Kaever V; Research Core Unit Metabolomics, Hannover Medical School, Hannover, Germany.
  • Givskov M; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Tolker-Nielsen T; Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore.
Microbiology (Reading) ; 162(10): 1797-1807, 2016 10.
Article em En | MEDLINE | ID: mdl-27526691
Current antibiotic treatments are insufficient in eradicating bacterial biofilms, which represent the primary cause of chronic bacterial infections. Thus, there is an urgent need for new strategies to eradicate biofilm infections. The second messenger c-di-GMP is a positive regulator of biofilm formation in many clinically relevant bacteria. It is hypothesized that drugs lowering the intracellular level of c-di-GMP will force biofilm bacteria into a more treatable planktonic lifestyle. To identify compounds capable of lowering c-di-GMP levels in Pseudomonas aeruginosa, we screened 5000 compounds for their potential c-di-GMP-lowering effect using a recently developed c-di-GMP biosensor strain. Our screen identified the anti-cancerous drug doxorubicin as a potent c-di-GMP inhibitor. In addition, the drug decreased the transcription of many biofilm-related genes. However, despite its effect on the c-di-GMP content in P. aeruginosa, doxorubicin was unable to inhibit biofilm formation or disperse established biofilms. On the contrary, the drug was found to promote P. aeruginosa biofilm formation, possibly through release of extracellular DNA from a subpopulation of killed bacteria. Our findings emphasize that lowering of the c-di-GMP content in bacteria might not be sufficient to mediate biofilm inhibition or dispersal.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pseudomonas aeruginosa / Doxorrubicina / GMP Cíclico / Biofilmes / Antineoplásicos Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pseudomonas aeruginosa / Doxorrubicina / GMP Cíclico / Biofilmes / Antineoplásicos Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article