Inactivation of the Pyrimidine Biosynthesis pyrD Gene Negatively Affects Biofilm Formation and Virulence Determinants in the Crohn’s Disease-Associated Adherent Invasive Escherichia coli LF82 Strain

Rossi, Elio; Leccese, Gabriella; Baldelli, Valerio; Bibi, Alessia; Scalone, Emanuele; Camilloni, Carlo; Paroni, Moira; Landini, Paolo

doi:10.3390/microorganisms10030537

Cited by 7 publications

(7 citation statements)

References 58 publications

(78 reference statements)

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“…Pyrimidine nucleotide degradation pyrimidine deoxyribonucleosides degradation as total sources of carbon and energy -Dihydroorotate dehydrogenase, an enzyme of the de novo pyrimidine biosynthetic pathway, strongly affects biofilm formation and promotes the ability of AIEC to grow in a macrophage (Rossi et al, 2022).…”

Section: Pwy0-1298mentioning

confidence: 99%

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Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn’s disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets

Khorsand

Aghdaei

Nazemalhosseini‐Mojarad

et al. 2022

Front. Cell. Infect. Microbiol.

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ObjectivesA number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn’s disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects.MethodsMetagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi’omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways.ResultsCompared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including Escherichia coli, Klebsiella variicola, Klebsiella quasipneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, and Citrobacter youngae, while Klebsiella oxytoca, Morganella morganii, and Citrobacter amalonaticus were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including Citrobacter portucalensis, Citrobacter pasteurii, Citrobacter werkmanii, and Proteus hauseri. Our analysis also showed a dramatically increased abundance of E. coli in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by E. coli were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to K. pneumoniae strains.ConclusionsIn conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly E. coli and Klebsiella species.

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Section: Pwy0-1298mentioning

confidence: 99%

“…-Intracellular pyrimidine concentrations act as a regulatory signal for genes involved in the virulence of AIEC strains (Rossi et al, 2022).…”

Section: Pwy0-1298mentioning

confidence: 99%

Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn’s disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets

Khorsand

Aghdaei

Nazemalhosseini‐Mojarad

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Thus, the ultimate impact of pyrimidine regulation during infection may be on sugar processing via UDP-glucose for capsule formation rather than solely pyrimidine availability for growth. However, pyrimidine biosynthesis has been shown essential for in vivo growth in several other bacterial pathogens, so the impact of inhibiting pyrimidine synthesis may be more widespread and not necessarily specific to S. pneumoniae capsule 87,88 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the fitness benefit conferred by RNA cis-regulators toStreptococcus pneumoniaeduring infection

Warrier,

Perry,

Hubbell

et al. 2023

Preprint

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Bacteria have evolved complex transcriptional regulatory networks, as well as many diverse regulatory strategies at the RNA level, to enable more efficient use of metabolic resources and rapid response to changing conditions. However, most RNA-based regulatory mechanisms are not well conserved across different bacterial species despite controlling genes important for virulence or essential biosynthetic processes. Here, we characterize the activity of, and assess the fitness benefit conferred by, twelve cis-acting regulatory RNAs (including several riboswitches and a T-box), in the opportunistic pathogenStreptococcus pneumoniaeTIGR4. By evaluating native locus mutants of each regulator that result in constitutively active and repressed expression, we establish that growth defects in planktonic culture are associated with constitutive repression of gene expression, while constitutive activation of gene expression is rarely deleterious. In contrast, in mouse nasal carriage and pneumonia models, strains with both constitutively active and repressed gene expression are significantly less fit than matched control strains. Furthermore, two RNA-regulated pathways, FMN synthesis/transport and pyrimidine synthesis/transport display the greatest sensitivity to mis-regulation or constitutive gene repression in both planktonic culture andin vivoenvironments. Our findings suggest that despite lack of an obvious phenotypes associated with gene over-expressionin vitro, the fitness benefit conferred on bacteria via fine-tuned metabolic regulation through cis-acting regulatory RNAs is often substantialin vivo, and therefore easily sufficient to drive the evolution and maintenance of diverse RNA regulatory mechanisms.

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“…Thus, the ultimate impact of pyrimidine regulation during infection may be on sugar processing via UDP-glucose for capsule formation rather than solely pyrimidine availability for growth. However, pyrimidine biosynthesis has been shown to be essential for in vivo growth in several other bacterial pathogens, so the impact of inhibiting pyrimidine synthesis may be more widespread and not necessarily specific to S. pneumoniae [88,89].…”

Section: Plos Geneticsmentioning

confidence: 99%

RNA cis-regulators are important for Streptococcus pneumoniae in vivo success

Warrier,

Perry,

Hubbell

et al. 2024

PLoS Genet

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Bacteria have evolved complex transcriptional regulatory networks, as well as many diverse regulatory strategies at the RNA level, to enable more efficient use of metabolic resources and a rapid response to changing conditions. However, most RNA-based regulatory mechanisms are not well conserved across different bacterial species despite controlling genes important for virulence or essential biosynthetic processes. Here, we characterize the activity of, and assess the fitness benefit conferred by, twelve cis-acting regulatory RNAs (including several riboswitches and a T-box), in the opportunistic pathogen Streptococcus pneumoniae TIGR4. By evaluating native locus mutants of each regulator that result in constitutively active or repressed expression, we establish that growth defects in planktonic culture are associated with constitutive repression of gene expression, while constitutive activation of gene expression is rarely deleterious. In contrast, in mouse nasal carriage and pneumonia models, strains with either constitutively active and repressed gene expression are significantly less fit than matched control strains. Furthermore, two RNA-regulated pathways, FMN synthesis/transport and pyrimidine synthesis/transport display exceptional sensitivity to mis-regulation or constitutive gene repression in both planktonic culture and in vivo environments. Thus, despite lack of obvious phenotypes associated with constitutive gene expression in vitro, the fitness benefit conferred on bacteria via fine-tuned metabolic regulation through cis-acting regulatory RNAs is substantial in vivo, and therefore easily sufficient to drive the evolution and maintenance of diverse RNA regulatory mechanisms.

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Inactivation of the Pyrimidine Biosynthesis pyrD Gene Negatively Affects Biofilm Formation and Virulence Determinants in the Crohn’s Disease-Associated Adherent Invasive Escherichia coli LF82 Strain

Cited by 7 publications

References 58 publications

Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn’s disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets

Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn’s disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets

Evaluation of the fitness benefit conferred by RNA cis-regulators toStreptococcus pneumoniaeduring infection

RNA cis-regulators are important for Streptococcus pneumoniae in vivo success

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