A computational model of Pseudomonas syringae metabolism unveils a role for branched-chain amino acids in Arabidopsis leaf colonization

PLoS Comput Biol. 2023 Dec 27;19(12):e1011651. doi: 10.1371/journal.pcbi.1011651. Online ahead of print. ABSTRACT Bacterial pathogens adapt their metabolism to the plant environment to successfully colonize their hosts. In our efforts to uncover the metabolic pathways that contribute to the colonization of Arabidopsis thaliana leaves by Pseudomonas syringae pv tomato DC3000 (Pst DC3000), we created iPst19, […]

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Model-driven characterization of functional diversity of Pseudomonas aeruginosa clinical isolates with broadly representative phenotypes

bioRxiv. 2023 Oct 10:2023.10.08.561426. doi: 10.1101/2023.10.08.561426. Preprint. ABSTRACT Pseudomonas aeruginosa is a leading cause of infections in immunocompromised individuals and in healthcare settings. This study aims to understand the relationships between phenotypic diversity and the functional metabolic landscape of P. aeruginosa clinical isolates. To better understand the metabolic repertoire of P. aeruginosa in infection, we […]

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Systems-ecology designed bacterial consortium protects from severe Clostridioides difficile infection

bioRxiv. 2023 Aug 10:2023.08.08.552483. doi: 10.1101/2023.08.08.552483. Preprint. ABSTRACT Fecal Microbiota Transplant (FMT) is an emerging therapy that has had remarkable success in treatment and prevention of recurrent Clostridioides difficile infection (rCDI). FMT has recently been associated with adverse outcomes such as inadvertent transfer of antimicrobial resistance, necessitating development of more targeted bacteriotherapies. To address this […]

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Metabolic modeling of sex-specific liver tissue suggests mechanism of differences in toxicological responses

PLoS Comput Biol. 2023 Aug 21;19(8):e1010927. doi: 10.1371/journal.pcbi.1010927. Online ahead of print. ABSTRACT Male subjects in animal and human studies are disproportionately used for toxicological testing. This discrepancy is evidenced in clinical medicine where females are more likely than males to experience liver-related adverse events in response to xenobiotics. While previous work has shown gene […]

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The blossoming of methods and software in computational biology

PLoS Comput Biol. 2023 Aug 17;19(8):e1011390. doi: 10.1371/journal.pcbi.1011390. eCollection 2023 Aug. NO ABSTRACT PMID:37590323 | DOI:10.1371/journal.pcbi.1011390

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Transcriptome-guided metabolic network analysis reveals rearrangements of carbon flux distribution in Neisseria gonorrhoeae during neutrophil co-culture

mSystems. 2023 Jun 30:e0126522. doi: 10.1128/msystems.01265-22. Online ahead of print. ABSTRACT The ability of bacterial pathogens to metabolically adapt to the environmental conditions of their hosts is critical to both colonization and invasive disease. Infection with Neisseria gonorrhoeae (the gonococcus, Gc) is characterized by the influx of neutrophils [polymorphonuclear leukocytes (PMNs)], which fail to clear […]

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Reconstructor: A COBRApy compatible tool for automated genome-scale metabolic network reconstruction with parsimonious flux-based gap-filling

Bioinformatics. 2023 Jun 5:btad367. doi: 10.1093/bioinformatics/btad367. Online ahead of print. ABSTRACT MOTIVATION: Genome-scale metabolic network reconstructions (GENREs) are valuable for understanding cellular metabolism in silico. Several tools exist for automatic GENRE generation. However, these tools frequently (1) do not readily integrate with some of the widely-used suites of packaged methods available for network analysis, (2) […]

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Network analysis of toxin production in Clostridioides difficile identifies key metabolic dependencies

PLoS Comput Biol. 2023 Apr 26;19(4):e1011076. doi: 10.1371/journal.pcbi.1011076. Online ahead of print. ABSTRACT Clostridioides difficile pathogenesis is mediated through its two toxin proteins, TcdA and TcdB, which induce intestinal epithelial cell death and inflammation. It is possible to alter C. difficile toxin production by changing various metabolite concentrations within the extracellular environment. However, it is […]

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Metabolic modeling of sex-specific tissue predicts mechanisms of differences in toxicological responses

bioRxiv. 2023 Feb 7:2023.02.07.527430. doi: 10.1101/2023.02.07.527430. Preprint. ABSTRACT Male subjects in animal and human studies are disproportionately used for toxicological testing. This discrepancy is evidenced in clinical medicine where females are more likely than males to experience liver-related adverse events in response to xenobiotics. While previous work has shown gene expression differences between the sexes, […]

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Identifying metabolic shifts in Crohn’s disease using’ omics-driven contextualized computational metabolic network models

Sci Rep. 2023 Jan 5;13(1):203. doi: 10.1038/s41598-022-26816-5. ABSTRACT Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. A clear gap in our existing CD diagnostics and current disease management approaches is the lack of highly specific biomarkers that can be used to streamline or personalize disease management. Comprehensive profiling of metabolites holds […]

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