A49 CO-INFECTION WITH PARASITIC WORMS ENHANCES THE ABILITY OF SALMONELLA TO COLONIZE THE GUT LUMEN AND DEWORMING RESTORES COLONIZATION RESISTANCE TO SALMONELLA
Bibliographic record
Abstract
Abstract Background Chronic infections with intestinal helminths occur primarily in world regions where infections with bacterial pathogens are also common. Research so far has shown that helminths can promote bacterial infection, however, the precise mechanisms of this are unknown. Current helminth control strategies involve mass deworming programs, and it is as yet unclear how deworming impacts susceptibility to bacterial infections in helminth-affected areas. Aims Our aims were to decipher the mechanistic details by which helminths can promote intestinal bacterial infection, and to determine how deworming affects susceptibility to intestinal colonization by bacterial pathogens. Methods Using a mouse model of enteric helminth-bacterial coinfection, we examined how the small intestinal helminth Heligmosomoides polygyrus promotes intestinal colonization by Salmonella enterica serovar Typhimurim. To study the effect of deworming of concurrent Salmonella infection, we treated our helminth-infected mice with the anthelmintic drug Strongid P both before and after Salmonella (co-) infection. To examine whether heightened Salmonella colonization during helminth infection depended on the ability of Salmonella to invade host tissue, we compared the ability of wild-type Salmonella or an invasion-deficient mutant (ΔinvA) to colonize during helminth co-infection. Results An ongoing helminth infection resulted in high levels of Salmonella in the small intestine after co-infection, however, when mice were dewormed prior to Salmonella co-infection, they were no longer susceptible to high small intestinal Salmonella burdens. In contrast, when helminth-infected mice are dewormed after Salmonella has already co-colonized, high Salmonella burdens persisted in the small intestine. Further, we found that during helminth co-infection, Salmonella primarily expands in the gut lumen rather than in the small intestinal tissue, and in line with this, a Salmonella invasion mutant was able to colonize the intestine to a similar extent to wild-type Salmonella during helminth infection. Conclusions Deworming experiments have revealed that the effects of H. polygyrus on promoting Salmonella colonization in the small intestines depend on the ongoing presence of the helminth. Deworming did not revert bacterial burdens once Salmonella had colonized, suggesting that an ongoing helminth infection reduces colonization resistance to Salmonella infection but was not required for Salmonella to persist after initial colonization by Salmonella. Further, we discovered that Salmonella expansion during helminth infection is independent of bacterial invasion of host tissue. Funding Agencies CIHR
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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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".