CaltechAUTHORS
  A Caltech Library Service

The Ferrous Iron-Responsive BqsRS Two-Component System Activates Genes That Promote Cationic Stress Tolerance

Kreamer, Naomi N. and Costa, Flavia and Newman, Dianne K. (2015) The Ferrous Iron-Responsive BqsRS Two-Component System Activates Genes That Promote Cationic Stress Tolerance. mBio, 6 (2). Art. No. e02549-14. ISSN 2150-7511. PMCID PMC4358008. http://resolver.caltech.edu/CaltechAUTHORS:20150619-085839244

[img] PDF - Published Version
Creative Commons Attribution Non-commercial Share Alike.

1119Kb
[img] PDF (Dataset sd1) - Supplemental Material
Creative Commons Attribution Non-commercial Share Alike.

87Kb
[img] PDF (Dataset sd2) - Supplemental Material
Creative Commons Attribution Non-commercial Share Alike.

77Kb
[img] PDF (Dataset sd3) - Supplemental Material
Creative Commons Attribution Non-commercial Share Alike.

68Kb
[img] PDF (Table st1) - Supplemental Material
Creative Commons Attribution Non-commercial Share Alike.

40Kb
[img] PDF (Table st2) - Supplemental Material
Creative Commons Attribution Non-commercial Share Alike.

59Kb
[img] PDF (Text s1) - Supplemental Material
Creative Commons Attribution Non-commercial Share Alike.

79Kb
[img] Image (TIFF) (Figure sf1) - Supplemental Material
Creative Commons Attribution Non-commercial Share Alike.

2932Kb
[img] Image (TIFF) (Figure sf2) - Supplemental Material
Creative Commons Attribution Non-commercial Share Alike.

2932Kb
[img] Image (TIFF) (Figure sf3) - Supplemental Material
Creative Commons Attribution Non-commercial Share Alike.

2932Kb
[img] Image (TIFF) (Figure sf4) - Supplemental Material
Creative Commons Attribution Non-commercial Share Alike.

2932Kb

Use this Persistent URL to link to this item: http://resolver.caltech.edu/CaltechAUTHORS:20150619-085839244

Abstract

The physiological resistance of pathogens to antimicrobial treatment is a severe problem in the context of chronic infections. For example, the mucus-filled lungs of cystic fibrosis (CF) patients are readily colonized by diverse antibiotic-resistant microorganisms, including Pseudomonas aeruginosa. Previously, we showed that bioavailable ferrous iron [Fe(II)] is present in CF sputum at all stages of infection and constitutes a significant portion of the iron pool at advanced stages of lung function decline [R. C. Hunter et al., mBio 4(4):e00557-13, 2013]. P. aeruginosa, a dominant CF pathogen, senses Fe(II) using a two-component signal transduction system, BqsRS, which is transcriptionally active in CF sputum [R. C. Hunter et al., mBio 4(4):e00557-13, 2013; N. N. Kreamer, J. C. Wilks, J. J. Marlow, M. L. Coleman, and D. K. Newman, J Bacteriol 194:1195–1204, 2012]. Here, we show that an RExxE motif in BqsS is required for BqsRS activation. Once Fe(II) is sensed, BqsR binds a tandem repeat DNA sequence, activating transcription. The BqsR regulon—defined through iterative bioinformatic predictions and experimental validation—includes several genes whose products are known to drive antibiotic resistance to aminoglycosides and polymyxins. Among them are genes encoding predicted determinants of polyamine transport and biosynthesis. Compared to the wild type, bqsS and bqsR deletion mutants are sensitive to high levels of Fe(II), produce less spermidine in high Fe(II), and are more sensitive to tobramycin and polymyxin B but not arsenate, chromate, or cefsulodin. BqsRS thus mediates a physiological response to Fe(II) that guards the cell against positively charged molecules but not negatively charged stressors. These results suggest Fe(II) is an important environmental signal that, via BqsRS, bolsters tolerance of a variety of cationic stressors, including clinically important antimicrobial agents.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1128/mBio.02549-14DOIArticle
http://mbio.asm.org/content/6/2/e02549-14PublisherArticle
http://mbio.asm.org/content/suppl/2015/02/24/mBio.02549-14.DCSupplementalPublisherSupplementary Data
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358008/PubMed CentralArticle
Additional Information:© 2015 Kreamer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Received 23 December 2014; Accepted 7 January 2015; Published 24 February 2015. We thank Megan Bergkessel, other members of the Newman laboratory, and anonymous reviewers for constructive comments on the manuscript. This work was supported by grants to D.K.N. from the Howard Hughes Medical Institute (HHMI) and the National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL117328) and by the Millard and Muriel Jacobs Genetics and Genomics Laboratory at California Institute of Technology. D.K.N. is an HHMI Investigator.
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
National Heart, Lung and Blood InstituteR01HL117328
Caltech Millard and Muriel Jacobs Genetics and Genomics LaboratoryUNSPECIFIED
PubMed Central ID:PMC4358008
Record Number:CaltechAUTHORS:20150619-085839244
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20150619-085839244
Official Citation:Kreamer NN, Costa F, Newman DK. 2015. The ferrous iron-responsive BqsRS two-component system activates genes that promote cationic stress tolerance. mBio 6(2):e02549-14. doi:10.1128/mBio.02549-14
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58364
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:19 Jun 2015 16:42
Last Modified:19 Jun 2015 16:42

Repository Staff Only: item control page