Pseudomonas aeruginosa lasR mutant fitness in microoxia is supported by an Anr-regulated oxygen-binding hemerythrin
Michelle E. Clay,
John H Hammond,
Caitlin H Kowalski,
Alexandra J. Lee,
Monique S. Porter,
Casey S. Greene,
Ekaterina V Pletneva,
Deborah A. Hogan
Posted 13 Oct 2019
bioRxiv DOI: 10.1101/802934 (published DOI: 10.1073/pnas.1917576117)
Posted 13 Oct 2019
Pseudomonas aeruginosa strains with loss-of-function mutations in the transcription factor are frequently encountered in the clinic and the environment. Among the characteristics common to LasR-defective (LasR-) strains is increased activity of the transcription factor Anr, relative to their LasR+ counterparts, in low oxygen conditions. One of the Anr-regulated genes that was highly induced in the LasR- strains encoded a putative oxygen-binding hemerythrin encoded by PA14_42860 ( PA1673 ) which we named mhr for microoxic hemerythrin. Purified P. aeruginosa Mhr protein contained the predicted di-iron center and binds oxygen with a Kd of 1 micromolar. Both Anr and Mhr were necessary for fitness in LasR+ and lasR mutant strains in colony biofilms grown in microoxic conditions, and the effects were more striking in the lasR mutant. Among genes in the Anr regulon, mhr was most closely co-regulated with the Anr-controlled high affinity cytochrome c oxidase genes and in the absence of high affinity cytochrome c oxidase activity, deletion of mhr no longer caused a fitness disadvantage suggesting that Mhr works in concert with microoxic respiration. We demonstrate that Anr and Mhr contribute to LasR- strain fitness even in the normoxic biofilm conditions, and metabolomics data indicate that in a lasR mutant, expression of Anr-regulated mhr leads to differences in metabolism in cells grown on LB and artificial sputum medium. Together these data indicate that increased Anr activity in microoxically-grown lasR mutants confers an advantage in part for its regulation of the O2 binding protein Mhr.
- Downloaded 167 times
- Download rankings, all-time:
- Site-wide: 80,844 out of 100,360
- In microbiology: 6,682 out of 8,897
- Year to date:
- Site-wide: 59,997 out of 100,360
- Since beginning of last month:
- Site-wide: None out of 100,360
Downloads over time
Distribution of downloads per paper, site-wide
- 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!