Protein allocation and utilization in the versatile chemolithoautotroph Cupriavidus necator
- Science for Life Laboratory, KTH - Royal Institute of Technology, Sweden
- The Broad Institute and Boston Children's Hospital, United States
- Heidelberg University, Germany
Abstract
Bacteria must balance the different needs for substrate assimilation, growth functions, and resilience in order to thrive in their environment. Of all cellular macromolecules, the bacterial proteome is by far the most important resource and its size is limited. Here, we investigated how the highly versatile 'knallgas' bacterium Cupriavidus necator reallocates protein resources when grown on different limiting substrates and with different growth rates. We determined protein quantity by mass spectrometry and estimated enzyme utilization by resource balance analysis modeling. We found that C. necator invests a large fraction of its proteome in functions that are hardly utilized. Of the enzymes that are utilized, many are present in excess abundance. One prominent example is the strong expression of CBB cycle genes such as Rubisco during growth on fructose. Modeling and mutant competition experiments suggest that CO2-reassimilation through Rubisco does not provide a fitness benefit for heterotrophic growth, but is rather an investment in readiness for autotrophy.
Data availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD024819. Protein quantification results can be browsed and interactively analyzed using the web application available at https://m-jahn.shinyapps.io/ShinyProt.Sequencing data for TnSeq and BarSeq experiments are available at the European Nucleotide Archive with accession number PRJEB43757. The data for competition experiments performed with the transposon mutant library can be browsed and interactively analyzed using the web application available at https://m-jahn.shinyapps.io/ShinyLib/.
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Gene fitness in the versatile chemolithoautotroph Cupriavidus necatorEuropean Nucleotide Archive, PRJEB43757.
Article and author information
Author details
Johannes Asplund-Samuelsson
Funding
Swedish Research Council Vetenskapsrådet (2016-06160)
- Nick Crang
- Kyle Kimler
- Johannes Asplund-Samuelsson
Swedish Research Council Formas (2019-01491)
- Michael Jahn
Swedish Research Council Formas (2015-939)
- Michael Jahn
Novo Nordisk Fonden (NNF20OC0061469)
- Markus Janasch
- Elton Paul Hudson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Gisela Storz, National Institute of Child Health and Human Development, United States
Version history
- Preprint posted: March 22, 2021 (view preprint)
- Received: April 1, 2021
- Accepted: October 30, 2021
- Accepted Manuscript published: November 1, 2021 (version 1)
- Version of Record published: November 11, 2021 (version 2)
- Version of Record updated: November 16, 2021 (version 3)
Copyright
© 2021, Jahn et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Protein allocation and utilization in the versatile chemolithoautotroph Cupriavidus necator
eLife 10:e69019.
https://doi.org/10.7554/eLife.69019
Further reading
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- Computational and Systems Biology
- Medicine
Background:
Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm birth occur spontaneously and result from preterm labor with intact (spontaneous preterm labor [sPTL]) or ruptured (preterm prelabor rupture of membranes [PPROM]) membranes. The prediction of spontaneous preterm birth (sPTB) remains underpowered due to its syndromic nature and the dearth of independent analyses of the vaginal host immune response. Thus, we conducted the largest longitudinal investigation targeting vaginal immune mediators, referred to herein as the immunoproteome, in a population at high risk for sPTB.
Methods:
Vaginal swabs were collected across gestation from pregnant women who ultimately underwent term birth, sPTL, or PPROM. Cytokines, chemokines, growth factors, and antimicrobial peptides in the samples were quantified via specific and sensitive immunoassays. Predictive models were constructed from immune mediator concentrations.
Results:
Throughout uncomplicated gestation, the vaginal immunoproteome harbors a cytokine network with a homeostatic profile. Yet, the vaginal immunoproteome is skewed toward a pro-inflammatory state in pregnant women who ultimately experience sPTL and PPROM. Such an inflammatory profile includes increased monocyte chemoattractants, cytokines indicative of macrophage and T-cell activation, and reduced antimicrobial proteins/peptides. The vaginal immunoproteome has improved predictive value over maternal characteristics alone for identifying women at risk for early (<34 weeks) sPTB.
Conclusions:
The vaginal immunoproteome undergoes homeostatic changes throughout gestation and deviations from this shift are associated with sPTB. Furthermore, the vaginal immunoproteome can be leveraged as a potential biomarker for early sPTB, a subset of sPTB associated with extremely adverse neonatal outcomes.
Funding:
This research was conducted by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS) under contract HHSN275201300006C. ALT, KRT, and NGL were supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.
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- Computational and Systems Biology
- Genetics and Genomics
Runs of homozygosity (ROH) segments, contiguous homozygous regions in a genome were traditionally linked to families and inbred populations. However, a growing literature suggests that ROHs are ubiquitous in outbred populations. Still, most existing genetic studies of ROH in populations are limited to aggregated ROH content across the genome, which does not offer the resolution for mapping causal loci. This limitation is mainly due to a lack of methods for the efficient identification of shared ROH diplotypes. Here, we present a new method, ROH-DICE, to find large ROH diplotype clusters, sufficiently long ROHs shared by a sufficient number of individuals, in large cohorts. ROH-DICE identified over 1 million ROH diplotypes that span over 100 SNPs and are shared by more than 100 UK Biobank participants. Moreover, we found significant associations of clustered ROH diplotypes across the genome with various self-reported diseases, with the strongest associations found between the extended HLA region and autoimmune disorders. We found an association between a diplotype covering the HFE gene and hemochromatosis, even though the well-known causal SNP was not directly genotyped or imputed. Using a genome-wide scan, we identified a putative association between carriers of an ROH diplotype in chromosome 4 and an increase in mortality among COVID-19 patients (P-value=1.82×10-11). In summary, our ROH-DICE method, by calling out large ROH diplotypes in a large outbred population, enables further population genetics into the demographic history of large populations. More importantly, our method enables a new genome-wide mapping approach for finding disease-causing loci with multi-marker recessive effects at a population scale.
