Salmonella-liberated dietary L-arabinose promotes expansion in superspreaders

Ruddle, Sarah; Massis, Liliana M.; Cutter, Alyssa C.; Monack, Denise M.

doi:10.1016/j.chom.2023.01.017

Cited by 17 publications

(9 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some of these include ethanolamine and 1,2-propanediol, which have been suggested to be important for Salmonella expansion over commensal microbes(18, 20, 22, 55). Additionally, higher energy carbon sources, such as mannitol, arabinose, and galactitol, have been studied in relation to intracellular survival, Salmonella expansion, or competition(4, 6, 23, 56).…”

Section: Resultsmentioning

confidence: 99%

Time resolved multi-omics reveals diverse metabolic strategies ofSalmonelladuring diet-induced inflammation

Kokkinias,

Sabag-Daigle,

Kim

et al. 2024

Preprint

View full text Add to dashboard Cite

With a rise in antibiotic resistance and chronic infection, the metabolic response of Salmonella enterica serovar Typhimurium to various dietary conditions over time remains an understudied avenue for novel, targeted therapeutics. Elucidating how enteric pathogens respond to dietary variation not only helps us decipher the metabolic strategies leveraged for expansion but also assists in proposing targets for therapeutic interventions. Here, we use a multi-omics approach to identify the metabolic response of Salmonella enterica serovar Typhimurium in mice on both a fibrous diet and high-fat diet over time. When comparing Salmonella gene expression between diets, we found a preferential use of respiratory electron acceptors consistent with increased inflammation of the high-fat diet mice. Looking at the high-fat diet over the course of infection, we noticed heterogeneity of samples based on Salmonella ribosomal activity, which separated into three infection phases: early, peak, and late. We identified key respiratory, carbon, and pathogenesis gene expression descriptive of each phase. Surprisingly, we identified genes associated with host-cell entry expressed throughout infection, suggesting sub-populations of Salmonella or stress-induced dysregulation. Collectively, these results highlight not only the sensitivity of Salmonella to its environment but also identify phase-specific genes that may be used as therapeutic targets to reduce infection.

show abstract

Section: Resultsmentioning

confidence: 99%

Time resolved multi-omics reveals diverse metabolic strategies ofSalmonelladuring diet-induced inflammation

Kokkinias,

Sabag-Daigle,

Kim

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Typhimurium promotes expansion in the gastrointestinal tract of mice 50 . This occurs via a mechanism involving an intrinsic alpha-N-arabinofuranosidase that liberates the sugar from dietary polysaccharides.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, while the canonical ʟ-arabinose utilisation pathway has been understood and exploited in bacterial genetics for decades, the relevance of ʟ-arabinose metabolism in promoting pathogenesis has only recently emerged. Dietary ʟ-arabinose utilisation by S. Typhimurium promotes expansion in the gastrointestinal tract of mice 50 . This occurs via a mechanism involving an intrinsic alpha- N -arabinofuranosidase that liberates the sugar from dietary polysaccharides.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of ʟ -arabinose converges with virulence regulation to promote enteric pathogen fitness

Cottam,

White,

Beck

et al. 2023

Preprint

View full text Add to dashboard Cite

Virulence and metabolism are often interlinked to control the expression of essential colonisation factors in response to host-associated signals. Here, we identified a novel transporter of the dietary monosaccharide ʟ-arabinose that is widely encoded by the zoonotic pathogen enterohaemorrhagicEscherichia coli(EHEC), required for full competitive fitness in the mouse gut and highly expressed during human infection. Accordingly, we discovered that ʟ-arabinose induces expression of the EHEC type 3 secretion system, enhancing its ability to attach to host cells, and that the underlying mechanism is dependent on products of its catabolism rather than the sensing of ʟ-arabinose as a signal. Finally, using the murine pathogenCitrobacter rodentium,we show that ʟ-arabinose metabolism provides a fitness benefit during enteric infection via virulence factor regulation, as opposed to supporting pathogen growth. This study describes an intrinsic mechanism of integrating central sugar metabolism with virulence regulation and highlights the unexpected impact that nutrient utilisation can have in enteric pathogens.

show abstract

“…Lastly, we examined S. Tm promoter activity during the escape stage of macrophage infection between 13-15 h.p.i., an interval during which macrophages undergo inflammasome-mediated pyroptosis 56 . The promoter for yihO, which encodes a membrane transport protein important for capsule assembly and environmental persistence 57 , turned ON during the later stages of infection (tON=13 h), as did araC, part of the L-arabinose utilization operon that is important for the carbohydrate metabolism in the gut environment 58 . In summary, mapping the dynamics of transcriptional regulation during macrophage infection corroborated previous findings regarding the early response of S. Tm to the intracellular environment 11,59,60 , and provided the precise timing of activation for promoters regulating the expression of virulence-related genes over each stage of infection.…”

Section: Salmonella Promoters Turn On In Multiple Stages During Macro...mentioning

confidence: 99%

Temporal profiling ofSalmonellatranscriptional dynamics during macrophage infection using a comprehensive reporter library

Nguyen,

Diaz,

Rajendram

et al. 2023

Preprint

View full text Add to dashboard Cite

The transcriptome ofSalmonella entericaserovar Typhimurium (S. Tm) dynamically responds to the rapid environmental shifts intrinsic toS.Tm lifestyle, exemplified by entry into theSalmonella-containing vacuole (SCV) within macrophages. IntracellularS. Tm must respond to the acidity of the SCV, accumulation of reactive oxygen/nitrogen species, and fluctuations in nutrient availability. Despite thorough RNA-seq-based investigations, the precise transcriptional timing of the expression of many secretion systems, metabolic pathways, and virulence effectors involved in infection has yet to be elucidated. Here, we construct a comprehensive library of GFP-reporter strains representing ∼3,000 computationally identifiedS.Tm promoter regions to study the dynamics of transcriptional regulation. We quantified promoter activity duringin vitrogrowth in defined and complex media and throughout the timeline of intracellular infection of RAW 246.7 macrophages. Using bulk measurements and single-cell imaging, we uncovered condition-specific transcriptional regulation and population-level heterogeneity in the activity of virulence-related promoters, including SPI2 genes such asssaRandssaG. We discovered previously unidentified transcriptional activity from 234 genes, including ones with novel activity during infection that are associated with pathogenecity islands and are involved in metabolism and metal homeostasis. Our library and data sets should provide powerful resources for systems-level interrogation ofSalmonellatranscriptional dynamics.

show abstract

Salmonella-liberated dietary L-arabinose promotes expansion in superspreaders

Cited by 17 publications

References 74 publications

Time resolved multi-omics reveals diverse metabolic strategies ofSalmonelladuring diet-induced inflammation

Time resolved multi-omics reveals diverse metabolic strategies ofSalmonelladuring diet-induced inflammation

Metabolism of ʟ -arabinose converges with virulence regulation to promote enteric pathogen fitness

Temporal profiling ofSalmonellatranscriptional dynamics during macrophage infection using a comprehensive reporter library

Contact Info

Product

Resources

About