ArticlePLoS genetics2012
Integrative genomic analysis identifies isoleucine and CodY as regulators of Listeria monocytogenes virulence.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 110 citations in OpenAlex.
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- Applications of genome-scale metabolic models to investigate microbial metabolic adaptations in response to genetic or environmental perturbations.Briefings in bioinformatics · 2023Review
- Common pathogenic bacteria-induced reprogramming of the host proteinogenic amino acids metabolism.Amino acids · 2023Review
- Integrating proteomic data with metabolic modeling provides insight into key pathways ofFrontiers in microbiology · 2023Article
- Genomic and pathogenicity islands ofFrontiers in molecular biosciences · 2023Review
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- CodY Is a Global Transcriptional Regulator Required for Virulence in Group BFrontiers in microbiology · 2022Article
- A Metzincin and TIMP-Like Protein Pair of a Phage Origin SensitizeMicroorganisms · 2021Article
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- Alternative σ Factors Regulate Overlapping as Well as Distinct Stress Response and Metabolic Functions inPathogens (Basel, Switzerland) · 2021Article
- Characterization of the roles of activated charcoal and Chelex in the induction of PrfA regulon expression in complex medium.PloS one · 2021Article
- Role of GlnR in Controlling Expression of Nitrogen Metabolism Genes inJournal of bacteriology · 2020Article
- Tetanus Toxin Synthesis is Under the Control of A Complex Network of Regulatory Genes inToxins · 2020Article
- Genome-wide identification of Listeria monocytogenes CodY-binding sites.Molecular microbiology · 2020Article
- Chitin Attenuates Expression ofFrontiers in microbiology · 2020Article
- Cross Talk between SigB and PrfA in Listeria monocytogenes Facilitates Transitions between Extra- and Intracellular Environments.Microbiology and molecular biology reviews : MMBR · 2019Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular bacterial pathogens are metabolically adapted to grow within mammalian cells. While these adaptations are fundamental to the ability to cause disease, we know little about the relationship between the pathogen's metabolism and virulence. Here we used an integrative Metabolic Analysis Tool that combines transcriptome data with genome-scale metabolic models to define the metabolic requirements of Listeria monocytogenes during infection. Twelve metabolic pathways were identified as differentially active during L. monocytogenes growth in macrophage cells. Intracellular replication requires de novo synthesis of histidine, arginine, purine, and branch chain amino acids (BCAAs), as well as catabolism of L-rhamnose and glycerol. The importance of each metabolic pathway during infection was confirmed by generation of gene knockout mutants in the respective pathways. Next, we investigated the association of these metabolic requirements in the regulation of L. monocytogenes virulence. Here we show that limiting BCAA concentrations, primarily isoleucine, results in robust induction of the master virulence activator gene, prfA, and the PrfA-regulated genes. This response was specific and required the nutrient responsive regulator CodY, which is known to bind isoleucine. Further analysis demonstrated that CodY is involved in prfA regulation, playing a role in prfA activation under limiting conditions of BCAAs. This study evidences an additional regulatory mechanism underlying L. monocytogenes virulence, placing CodY at the crossroads of metabolism and virulence.
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