Key Players and Individualists of Cyclic-di-GMP Signaling in Burkholderia cenocepacia

Anja M Richter; Mustafa Fazli; Nadine Schmid; Rebecca Shilling; Angela Suppiger; Michael Givskov; Leo Eberl; Tim Tolker-Nielsen

doi:10.3389/fmicb.2018.03286

Key Players and Individualists of Cyclic-di-GMP Signaling in Burkholderia cenocepacia

Anja M Richter, Mustafa Fazli, Nadine Schmid, Rebecca Shilling, Angela Suppiger, Michael Givskov, Leo Eberl, Tim Tolker-Nielsen

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Abstract

Burkholderia cenocepacia H111 is an opportunistic pathogen associated with chronic lung infections in cystic fibrosis patients. Biofilm formation, motility and virulence of B. cenocepacia are regulated by the second messenger cyclic di-guanosine monophosphate (c-di-GMP). In the present study, we analyzed the role of all 25 putative c-di-GMP metabolizing proteins of B. cenocepacia H111 with respect to motility, colony morphology, pellicle formation, biofilm formation, and virulence. We found that RpfR is a key regulator of c-di-GMP signaling in B. cenocepacia, affecting a broad spectrum of phenotypes under various environmental conditions. In addition, we identified Bcal2449 as a regulator of B. cenocepacia virulence in Galleria mellonella larvae. While Bcal2449 consists of protein domains that may catalyze both c-di-GMP synthesis and degradation, only the latter was essential for larvae killing, suggesting that a decreased c-di-GMP level mediated by the Bcal2449 protein is required for virulence of B. cenocepacia. Finally, our work suggests that some individual proteins play a role in regulating exclusively motility (CdpA), biofilm formation (Bcam1160) or both (Bcam2836).

Original language	English
Article number	3286
Journal	Frontiers in Microbiology
Volume	9
Number of pages	15
ISSN	1664-302X
DOIs	https://doi.org/10.3389/fmicb.2018.03286
Publication status	Published - 2019

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Key Players and Individualists of Cyclic-di-GMP Signaling in Burkholderia cenocepaciaFinal published version, 2.43 MBLicence: CC BY

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title = "Key Players and Individualists of Cyclic-di-GMP Signaling in Burkholderia cenocepacia",

abstract = "Burkholderia cenocepacia H111 is an opportunistic pathogen associated with chronic lung infections in cystic fibrosis patients. Biofilm formation, motility and virulence of B. cenocepacia are regulated by the second messenger cyclic di-guanosine monophosphate (c-di-GMP). In the present study, we analyzed the role of all 25 putative c-di-GMP metabolizing proteins of B. cenocepacia H111 with respect to motility, colony morphology, pellicle formation, biofilm formation, and virulence. We found that RpfR is a key regulator of c-di-GMP signaling in B. cenocepacia, affecting a broad spectrum of phenotypes under various environmental conditions. In addition, we identified Bcal2449 as a regulator of B. cenocepacia virulence in Galleria mellonella larvae. While Bcal2449 consists of protein domains that may catalyze both c-di-GMP synthesis and degradation, only the latter was essential for larvae killing, suggesting that a decreased c-di-GMP level mediated by the Bcal2449 protein is required for virulence of B. cenocepacia. Finally, our work suggests that some individual proteins play a role in regulating exclusively motility (CdpA), biofilm formation (Bcam1160) or both (Bcam2836).",

author = "Richter, {Anja M} and Mustafa Fazli and Nadine Schmid and Rebecca Shilling and Angela Suppiger and Michael Givskov and Leo Eberl and Tim Tolker-Nielsen",

year = "2019",

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language = "English",

volume = "9",

journal = "Frontiers in Microbiology",

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T1 - Key Players and Individualists of Cyclic-di-GMP Signaling in Burkholderia cenocepacia

AU - Richter, Anja M

AU - Fazli, Mustafa

AU - Schmid, Nadine

AU - Shilling, Rebecca

AU - Suppiger, Angela

AU - Givskov, Michael

AU - Eberl, Leo

AU - Tolker-Nielsen, Tim

PY - 2019

Y1 - 2019

N2 - Burkholderia cenocepacia H111 is an opportunistic pathogen associated with chronic lung infections in cystic fibrosis patients. Biofilm formation, motility and virulence of B. cenocepacia are regulated by the second messenger cyclic di-guanosine monophosphate (c-di-GMP). In the present study, we analyzed the role of all 25 putative c-di-GMP metabolizing proteins of B. cenocepacia H111 with respect to motility, colony morphology, pellicle formation, biofilm formation, and virulence. We found that RpfR is a key regulator of c-di-GMP signaling in B. cenocepacia, affecting a broad spectrum of phenotypes under various environmental conditions. In addition, we identified Bcal2449 as a regulator of B. cenocepacia virulence in Galleria mellonella larvae. While Bcal2449 consists of protein domains that may catalyze both c-di-GMP synthesis and degradation, only the latter was essential for larvae killing, suggesting that a decreased c-di-GMP level mediated by the Bcal2449 protein is required for virulence of B. cenocepacia. Finally, our work suggests that some individual proteins play a role in regulating exclusively motility (CdpA), biofilm formation (Bcam1160) or both (Bcam2836).

AB - Burkholderia cenocepacia H111 is an opportunistic pathogen associated with chronic lung infections in cystic fibrosis patients. Biofilm formation, motility and virulence of B. cenocepacia are regulated by the second messenger cyclic di-guanosine monophosphate (c-di-GMP). In the present study, we analyzed the role of all 25 putative c-di-GMP metabolizing proteins of B. cenocepacia H111 with respect to motility, colony morphology, pellicle formation, biofilm formation, and virulence. We found that RpfR is a key regulator of c-di-GMP signaling in B. cenocepacia, affecting a broad spectrum of phenotypes under various environmental conditions. In addition, we identified Bcal2449 as a regulator of B. cenocepacia virulence in Galleria mellonella larvae. While Bcal2449 consists of protein domains that may catalyze both c-di-GMP synthesis and degradation, only the latter was essential for larvae killing, suggesting that a decreased c-di-GMP level mediated by the Bcal2449 protein is required for virulence of B. cenocepacia. Finally, our work suggests that some individual proteins play a role in regulating exclusively motility (CdpA), biofilm formation (Bcam1160) or both (Bcam2836).

U2 - 10.3389/fmicb.2018.03286

DO - 10.3389/fmicb.2018.03286

M3 - Journal article

C2 - 30687272

SN - 1664-302X

VL - 9

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

M1 - 3286

ER -

Key Players and Individualists of Cyclic-di-GMP Signaling in Burkholderia cenocepacia

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