Genome-scale reconstruction of the Streptococcus pyogenes M49 metabolic network reveals growth requirements and indicates potential drug targets

Levering, Jennifer; Fiedler, Tomas; Sieg, Antje; Grinsven, Koen W.A. van; Hering, Silvio; Veith, Nadine; Olivier, Brett G.; Klett, Lara; Hugenholtz, Jeroen; Teusink, Bas; Kreikemeyer, Bernd; Kummer, Ursula

doi:10.1016/j.jbiotec.2016.01.035

Cited by 22 publications

(24 citation statements)

References 48 publications

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“…This same phylogenetic group is also characterized by extensive gene loss, presumably because the ancestor underwent a lifestyle switch from being mostly free-living to a host-associated lifestyle 56,57 . Loss was particularly common among genes underlying biosynthetic pathways; not surprisingly, many lactic acid bacteria are therefore auxotrophic for methionine synthesis, including Lactococcus lactis 9,58 , Lactobacillus plantarum 9 , Lactobacillus helveticus 59 , Streptococcus pyogenes 60 , Streptococcus thermophilus 61 , and Enterococcus faecalis 62 . In accordance with this lifestyle switch, the lactic acid bacteria are also characterized by an exceptional broad repertoire of carbon and amino acid transporters 56 , indicating that these bacteria often live in nutrient-rich environments.…”

Section: Discussionmentioning

confidence: 99%

A riboswitch gives rise to multi-generational phenotypic heterogeneity in an auxotrophic bacterium

2020

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Auxotrophy, the inability to produce an organic compound essential for growth, is widespread among bacteria. Auxotrophic bacteria rely on transporters to acquire these compounds from their environment. Here, we study the expression of both low-and high-affinity transporters of the costly amino acid methionine in an auxotrophic lactic acid bacterium, Lactococcus lactis. We show that the high-affinity transporter (Met-transporter) is heterogeneously expressed at low methionine concentrations, resulting in two isogenic subpopulations that sequester methionine in different ways: one subpopulation primarily relies on the high-affinity transporter (high expression of the Met-transporter) and the other subpopulation primarily relies on the low-affinity transporter (low expression of the Met-transporter). The phenotypic heterogeneity is remarkably stable, inherited for tens of generations, and apparent at the colony level. This heterogeneity results from a T-box riboswitch in the promoter region of the met operon encoding the high-affinity Met-transporter. We hypothesize that T-box riboswitches, which are commonly found in the Lactobacillales, may play as-yet unexplored roles in the predominantly auxotrophic lifestyle of these bacteria.

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Section: Discussionmentioning

confidence: 99%

A riboswitch gives rise to multi-generational phenotypic heterogeneity in an auxotrophic bacterium

2020

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“…Indeed, characteristic 13 C labelling patterns in threonine confirmed its synthesis via PEP, oxaloacetate and aspartate . Threonine biosynthesis in S. pyogenes seems not to be possible, even if strain differences are described . Remarkably, isotopologue profiling experiments in S. pneumoniae and S. suis revealed highest relative de novo biosynthesis rates of all synthesized amino acids for alanine, aspartate and threonine indicating a similar glycolytic flux in both species .…”

Section: The Central Metabolism Of Streptococcimentioning

confidence: 92%

“…A similar approach conducted with S. suis failed to detect labelled glutamate . Accordingly, S. suis cannot grow when glutamate and glutamine were simultaneously omitted from chemically defined growth media, an observation that has also been made in S. pyogenes and S. pneumoniae . In order to compensate the lack of glutamate biosynthesis and to satisfy a high demand of glutamate for transamination reactions, it is not surprising that these streptococci carry a least four different glutamine transporters in their genomes.…”

Section: The Central Metabolism Of Streptococcimentioning

confidence: 99%

Metabolic traits of pathogenic streptococci

Willenborg

Goethe

2016

FEBS Letters

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Edited by Wilhelm JustInvasive and noninvasive diseases caused by facultative pathogenic streptococci depend on their equipment with virulence factors and on their ability to sense and adapt to changing nutrients in different host environments. The knowledge of the principal metabolic mechanisms which allow these bacteria to recognize and utilize nutrients in host habitats is a prerequisite for our understanding of streptococcal pathogenicity and the development of novel control strategies. This review aims to summarize and compare the central carbohydrate metabolic and amino acid biosynthetic pathways of a selected group of streptococcal species, all belonging to the naso-oropharyngeal microbiome in humans and/or animals. We also discuss the urgent need of comprehensive metabolomics approaches for a better understanding of the streptococcal metabolism during host-pathogen interaction.

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“…This is because S. oralis does not colonize the nasopharynx and is usually not considered a pneumonia-causing agent like S. pneumoniae (Shah et al, 2011). The biomass reaction of iCJ415 is also similar to that of a S. pyogenes GEM (Levering et al, 2016). However, S. pyogenes, contains a capsule while S. oralis SK141 does not.…”

Section: Biomass Reactionmentioning

confidence: 99%

“…However, only two GEMs for human pathogenic streptococci have been published so far. One is for Streptococcus pyogenes, a distant relative of the MGS with a very different disease spectrum (Jensen and Kilian, 2012;Levering et al, 2016). The other published GEM is for a closer relative, Streptococcus pneumoniae (Dias et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Reconstruction and Validation of a Genome-Scale Metabolic Model of Streptococcus oralis (iCJ415), a Human Commensal and Opportunistic Pathogen

et al. 2020

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The mitis group of streptococci (MGS) is a member of the healthy human microbiome in the oral cavity and upper respiratory tract. Troublingly, some MGS are able to escape this niche and cause infective endocarditis, a severe and devastating disease. Genome-scale models have been shown to be valuable in investigating metabolism of bacteria. Here we present the first genome-scale model, iCJ415, for Streptococcus oralis SK141. We validated the model using gene essentiality and amino acid auxotrophy data from closely related species. iCJ415 has 71-76% accuracy in predicting gene essentiality and 85% accuracy in predicting amino acid auxotrophy. Further, the phenotype of S. oralis was tested using the Biolog Phenotype microarrays, giving iCJ415 a 82% accuracy in predicting carbon sources. iCJ415 can be used to explore the metabolic differences within the MGS, and to explore the complicated metabolic interactions between different species in the human oral cavity.

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Genome-scale reconstruction of the Streptococcus pyogenes M49 metabolic network reveals growth requirements and indicates potential drug targets

Cited by 22 publications

References 48 publications

A riboswitch gives rise to multi-generational phenotypic heterogeneity in an auxotrophic bacterium

A riboswitch gives rise to multi-generational phenotypic heterogeneity in an auxotrophic bacterium

Metabolic traits of pathogenic streptococci

Reconstruction and Validation of a Genome-Scale Metabolic Model of Streptococcus oralis (iCJ415), a Human Commensal and Opportunistic Pathogen

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