The anti-cancerous drug doxorubicin decreases the c-di-GMP content in Pseudomonas aeruginosa but promotes biofilm formation
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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.
In: Microbiology, Vol. 162, No. 10, 01.10.2016, p. 1797-1807.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The anti-cancerous drug doxorubicin decreases the c-di-GMP content in Pseudomonas aeruginosa but promotes biofilm formation
AU - Groizeleau, Julie
AU - Rybtke, Morten
AU - Andersen, Jens Bo
AU - Berthelsen, Jens
AU - Liu, Yang
AU - Yang, Liang
AU - Nielsen, Thomas E.
AU - Kaever, Volkhard
AU - Givskov, Michael
AU - Tolker-Nielsen, Tim
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
KW - Biofilm dispersal
KW - Biofilm inhibition
KW - c-di-GMP
KW - Doxorubicin
KW - Pseudomonas aeruginosa
U2 - 10.1099/mic.0.000354
DO - 10.1099/mic.0.000354
M3 - Journal article
C2 - 27526691
AN - SCOPUS:84992679375
VL - 162
SP - 1797
EP - 1807
JO - Microbiology
JF - Microbiology
SN - 1350-0872
IS - 10
ER -
ID: 169080499