A295 FUCOSE AVAILABILITY AND ITS UTILIZATION IMPACT IN VIVOENTERIC PATHOGEN VIRULENCE.
Bibliographic record
Abstract
Attaching and effacing (A/E) pathogens such as Enterohemorrhagic E. coli (EHEC) are important causes of diarrheal disease worldwide. Interestingly, little is known about how these bacteria obtain key nutrients, and whether these nutrients modulate pathogen colonization and gut infection. For example, fucose is an important sugar and bacterial food source cleaved from host glycans found on the intestinal mucosal surface via the actions of commensal microbes expressing fucosidase enzymes. Interestingly, although the mouse A/E pathogen Citrobacter rodentium does not itself express a fucosidase, recent studies have found that it and EHEC use a fucose sensing system to modulate their pathogenicity in vitro. At present, it is unclear what role fucose metabolism may play in A/E pathogen virulence and metabolism in vivo. To address this, we focused on C. rodentium enzyme L-fuculose kinase (encoded by the fucK gene), which plays a key role in the L-fucose metabolic pathway and fucose utilization as a food source. We investigated the roles of fucose and the enzyme L-fuculose kinase in controlling C. rodentium pathogenesis. Wildtype (WT) and ΔfucK C. rodentium were used for in vitro assays (type three secretion, growth and adhesion assays) and for in vivo infection. C57Bl/6 mice were infected either separately, or with both C. rodentium strains at a dose of 10^8 colony forming units. In some infections, mice were pretreated with streptomycin (20mg 24h pre-infection) or were fed fucose (200ul of 25mM L-fucose 2x/day). Bacterial burdens, pathology score and competitive assay were assessed on day 6 post-infection. In vitro virulence assays identified no significant differences between ΔfucK and WT C. rodentium regarding type three secretion, growth or adherence to cultured epithelial cells. Moreover, both WT and ΔfucK C. rodentium readily colonized the intestines of mice either pretreated (or not), with streptomycin, with pathogen burdens, localisation and histological pathology scores similar between the two strains. In contrast, simultaneous infection by both strains (competitive assay) within the same mice revealed the ΔfucK strain was significantly impaired when competing with WT C. rodentium (no streptomycin). In contrast, ΔfucK was able to equally compete with WT C. rodentium when streptomycin pretreatment was given to deplete commensal bacteria. Feeding fucose to these streptomycin treated mice again reduced the ability of the ΔfucK strain to compete with WT C. rodentium. These results indicate that the fucK-dependent fucose metabolic pathway promotes but is not essential to C. rodentium pathogenesis. Moreover these findings suggest that commensal microbes play a key role in controlling fucose availability in the gut, and thereby impact A/E pathogen metabolism and virulence. CCC, CIHRNSERC, FRQS
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".