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Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2018.00056

A c-di-GMP-modulating protein regulates swimming motility of Burkholderia cenocepacia in response to arginine and glutamate

Brijesh Kumar1, John L. Sorensen2 and  Silvia T. Cardona1, 3*
  • 1Microbiology, Faculty of Science, University of Manitoba, Canada
  • 2Chemistry, Faculty of Science, University of Manitoba, Canada
  • 3Medical Microbiology & Infection disease, Max Rady College of Medicine ,University of Manitoba, Canada

Burkholderia cenocepacia is an opportunistic bacterium that can thrive in different environments, including the amino acid-rich mucus of the cystic fibrosis (CF) lung. B. cenocepacia responds to the nutritional conditions that mimic the CF sputum by increasing flagellin expression and swimming motility. Individual amino acids also induce swimming but not flagellin expression. Here, we show that modulation of the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) levels by the PAS-containing c-di-GMP phosphodiesterase, BCAL1069 (CdpA), regulates the swimming motility of B. cenocepacia K56-2 in response to CF sputum nutritional conditions. Heterologous expression of WspR, a diguanylate cyclase, in B. cenocepacia K56-2 caused an increase in c-di-GMP levels and reduced swimming motility but did not affect flagellin expression or flagellar biosynthesis. After insertional mutagenesis of twelve putative genes encoding c-di-GMP metabolizing enzymes, one mutant of the locus BCAL1069 (cdpA), exhibited decreased swimming motility independent of flagellin expression in CF sputum nutritional conditions and an increase in intracellular c-di-GMP levels. The reduced swimming motility phenotype of the BCAL1069 mutant was observed in the presence of arginine and glutamate, but not of histidine, phenylalanine or proline. The B. cenocepacia CdpA was also found to be involved in regulation of protease activity but not in biofilm formation. Altogether, these results highlight a role of B. cenocepacia BCAL1069 (CdpA) in sensing the nutritional conditions of the CF sputum and eliciting a pathogenic response that includes swimming motility towards amino acids and an increase in protease activity.

Keywords: Cystic Fibrosis, SCFM, Burkholderia cenocepacia, c-di-GMP, Swimming, motility, BCAL1069, CDPA, Burkholderia cepacia complex

Received: 12 Nov 2017; Accepted: 12 Feb 2018.

Edited by:

Amal O. Amer, Department of Internal Medicine, Wexner Medical Center, Ohio State University, United States

Reviewed by:

Dinesh Sriramulu, Shres Consultancy (Life Sciences), India
Wenli Chen, Huazhong Agricultural University, China  

Copyright: © 2018 Kumar, Sorensen and Cardona. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Silvia T. Cardona, Faculty of Science, University of Manitoba, Microbiology, Winnipeg, Canada,