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Large metabolic rewiring from small genomic changes between strains of .

作者信息

Doore Sarah M, Subramanian Sundharraman, Tefft Nicholas M, Morona Renato, TerAvest Michaela A, Parent Kristin N

机构信息

Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.

School of Molecular and Biomedical Science, University of Adelaide, 5005 SA, Australia.

出版信息

J Bacteriol. 2021 Jun 1;203(11). doi: 10.1128/JB.00056-21. Epub 2021 Mar 22.


DOI:10.1128/JB.00056-21
PMID:33753469
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8117524/
Abstract

The instability of genomes has been described, but how this instability causes phenotypic differences within the species is largely unknown and likely variable. We describe herein the genome of strain PE577, originally a clinical isolate, which exhibits several phenotypic differences compared to the model strain 2457T. Like many previously described strains of , PE577 lacks discernible, functional CRISPR and restriction-modification systems. Its phenotypic differences when compared to 2457T include lower transformation efficiency, higher oxygen sensitivity, altered carbon metabolism, and greater susceptibility to a wide variety of lytic bacteriophage isolates. Since relatively few phages have been isolated on 2457T or the previously characterized strain M90T, developing a more universal model strain for isolating and studying phages is critical to understanding both phages and phage-host interactions. In addition to phage biology, the genome sequence of PE577 was used to generate and test hypotheses of how pseudogenes in this strain-whether interrupted by degraded prophages, transposases, frameshifts, or point mutations-have led to metabolic rewiring compared to the model strain 2457T. Results indicate that PE577 can utilise the less-efficient pyruvate oxidase/acetyl-CoA synthetase (PoxB/Acs) pathway to produce acetyl-CoA, while strain 2457T cannot due to a nonsense mutation in , rendering it a pseudogene in this strain. Both strains also utilize pyruvate-formate lyase to oxidize formate but cannot survive with this pathway alone, possibly because a component of the formate-hydrogen lyase () is a pseudogene in both strains. causes millions of dysentery cases worldwide, primarily affecting children under five years old. Despite active research in developing vaccines and new antibiotics, relatively little is known about the variation of physiology or metabolism across multiple isolates. In this work, we investigate two strains of that share 98.9% genetic identity but exhibit drastic differences in metabolism, ultimately affecting the growth of the two strains. Results suggest additional strains within the species utilize different metabolic pathways to process pyruvate. Metabolic differences between these closely-related isolates suggest an even wider variety of differences in growth across and in general. Exploring this variation further may assist the development or application of vaccines and therapeutics to combat infections.

摘要

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本文引用的文献

[1]
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[2]
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Formate Promotes Intercellular Spread and Virulence Gene Expression.

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PCR-Based Analysis of ColE1 Plasmids in Clinical Isolates and Metagenomic Samples Reveals Their Importance as Gene Capture Platforms.

Front Microbiol. 2018-3-16

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Shigella Phages Isolated during a Dysentery Outbreak Reveal Uncommon Structures and Broad Species Diversity.

J Virol. 2018-3-28

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Comprehensive analysis of central carbon metabolism illuminates connections between nutrient availability, growth rate, and cell morphology in Escherichia coli.

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Impact of Membrane Phospholipid Alterations in Escherichia coli on Cellular Function and Bacterial Stress Adaptation.

J Bacteriol. 2017-6-13

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