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

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

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.03286

DOI=10.3389/fmicb.2018.03286

ISSN=1664-302X

ABSTRACT=<p><italic>Burkholderia cenocepacia</italic> H111 is an opportunistic pathogen associated with chronic lung infections in cystic fibrosis patients. Biofilm formation, motility and virulence of <italic>B. cenocepacia</italic> 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 <italic>B. cenocepacia</italic> 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 <italic>B. cenocepacia</italic>, affecting a broad spectrum of phenotypes under various environmental conditions. In addition, we identified Bcal2449 as a regulator of <italic>B. cenocepacia</italic> virulence in <italic>Galleria mellonella</italic> 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 <italic>B. cenocepacia</italic>. Finally, our work suggests that some individual proteins play a role in regulating exclusively motility (CdpA), biofilm formation (Bcam1160) or both (Bcam2836).</p>