Endogenous Enterobacteriaceae underlie variation in susceptibility to Salmonella infection

Velazquez, Eric M.; Nguyen, Henry; Heasley, Keaton T.; Saechao, Cheng; Gil, Lindsey M.; Rogers, Alisdair; Miller, Brittany; Rolston, Matthew; Lopez, Christopher A.; Litvak, Yael; Liou, Megan J.; Faber, Franziska; Bronner, Denise N.; Tiffany, Connor R.; Byndloss, Mariana X.; Byndloss, Austin J.; Bäumler, Andreas J.

doi:10.1038/s41564-019-0407-8

Cited by 171 publications

(178 citation statements)

References 31 publications

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“…134,168,195,209 When known, relevant genetic variants exist, for example, in metabolism, specimens for genetic analyses should at least be collected and saved. • Age, sex, race/ethnicity, body size and composition, health status (especially with respect to outcomes of interest), co-medications, smoking, geography.…”

Section: Post-trial Interpretation Of Resultsmentioning

confidence: 99%

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Improving natural product research translation: From source to clinical trial

et al. 2019

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While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a Septe mber, 2018 trans disci plina ry workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research. K E Y W O R D S clinical predictive validity, dietary supplements, model systems, rigor and replicability, value of information | 43 SORKIN et al.still provide invaluable guidance, the results of such trials are often met with concerns that different design choiceswhether of product, dose, timing, participant eligibility criteria, outcomes, etc.-might have yielded a substantially different result. Each interventional trial represents a substantial investment, with well-powered Phase III CTs typically consuming more than $10 million and many person-years. 9,10 Additionally, as time and funds are limited, and participant pools may also be constrained, a decision to invest in a CT often precludes pursuing other research questions, 11 which may provide more useful public health-relevant knowledge than an RCT with an insufficient evidence base.

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Section: Post-trial Interpretation Of Resultsmentioning

confidence: 99%

“…190,191 These effects are modulated by sex in organisms ranging from fish and mice through humans. 168 Good practices for characterization of the gut microbiota have been discussed elsewhere. In addition, changes in the gut microbiota may exert separate direct or indirect effects on animal biology and health.…”

Section: Model-and Context-related Considerationsmentioning

confidence: 99%

Improving natural product research translation: From source to clinical trial

et al. 2019

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“…For example, animals of the same strain, but from different sources, or animals obtained from the same source but at different times, may be genetically different [17]. The immune or microbiological status of the animals can also influence welfare, experimental variability and scientific outcomes [106][107][108].…”

Section: Explanationmentioning

confidence: 99%

Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019

Sert

Ahluwalia

Alam³

et al. 2019

Preprint

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Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting are vital to this process; it allows readers to assess the reliability of the findings, and repeat or build upon the work of other researchers. The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments.Despite widespread endorsement by the scientific community, the impact of the ARRIVE guidelines on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This Explanation and Elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2019, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature.As a new international working groupthe authors of this publication, we have revised the guidelines to update them and facilitate their uptake; the ARRIVE guidelines 2019 are published alongside this paper [13]. We have updated the recommendations in line with current best practice, reorganised the information and classified the items into two sets. The ARRIVE Essential 10 constitute the minimum reporting requirement and the Recommended Set provides further context to the study described. The two sets help authors, journal staff, editors and reviewers use the guidelines in practice, and allow a pragmatic implementation with an initial focus on the most critical issues. Once the Essential 10 are consistently reported in manuscripts, items from the Recommended Set can be added to journal requirements over time until all 21 items are routinely reported in all manuscripts. Full methodology for the revision and the allocation of items into sets is described in the accompanying publication [13].A key aspect of the revision was to develop this Explanation and Elaboration document to provide background and rationale for each of the 21 items of ARRIVE 2019. Here we present additional guidance for each item and subitem, explain the importance of reporting this information in manuscripts that describe animal research, elaborate on what to report, and provide supporting evidence. Each subitem is also illustrated with examples of good reporting from the published literature. Box 1: GlossaryBias: Introduction of a systematic error in the estimated effect of an intervention, caused by inadequacies in the design, conduct, or analysis of an experiment.Effect size: Quantitative measure that estimates the magnitude of differences between groups, or relationships between variables. Experimental unit:Biological entity subjected to an intervention independently of all other units, such that it is possible to assign any two experimental units to different t...

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“…Exposure to antibiotics was not associated with Kp colonization or subsequent infection in our intensive care unit patient population 1,18 , indicating that Kp must contend with the indigenous microbiota to colonize the gut and cause infection. Previous studies have shown that gut microbiota differs by mouse vendor and by the room within each vendor facility (referred to as "barrier") 19 and these differences can impact experimental output [20][21][22] . Therefore, C57BL/6J mice were sourced from two different barriers (RB16 and RB07) at The Jackson Laboratory and inoculated orally with a mixture of wild-type and terC Kp (Fig.…”

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confidence: 99%

A plasmid locus associated withKlebsiellaclinical infections encodes a microbiome-dependent gut fitness factor

Vornhagen

Bassis

Ramakrishnan

et al. 2020

Preprint

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Introductory paragraphGut colonization by the pathogen Klebsiella pneumoniae (Kp) is consistently associated with subsequent Kp disease 1-5 , and patients are predominantly infected with their colonizing strain 1,2 . However, colonizing strains likely vary in their potential to cause infection. We previously identified the plasmid-encoded tellurium resistance (ter) operon as highly associated with infection when compared to asymptomatic colonization in hospitalized patients 1 . The ter operon bestows resistance to the toxic compound tellurite oxide (TeO3 -2 ), but this is unlikely to be its physiological function, as tellurium and TeO3 -2 are exceedingly rare. Here we show that terC is necessary and terZABCDEF is sufficient for phenotypic TeO3 -2 resistance. Next, we demonstrate that ter is encoded on a diverse group of plasmids without known plasmid-encoded virulence genes, suggesting an independent role in infection. Finally, our studies indicate that ter is a gut fitness factor, and its fitness advantage is conferred only when specific gut microbiota constituents are present. Collectively, these data reveal the Kp ter operon that is highly associated with human infection likely acts early in pathogenesis as a horizontally-transferrable fitness factor promoting robust gut colonization in the presence of the indigenous microbiota.3

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Endogenous Enterobacteriaceae underlie variation in susceptibility to Salmonella infection

Cited by 171 publications

References 31 publications

Improving natural product research translation: From source to clinical trial

Improving natural product research translation: From source to clinical trial

Reporting animal research: Explanation and Elaboration for the ARRIVE guidelines 2019

A plasmid locus associated withKlebsiellaclinical infections encodes a microbiome-dependent gut fitness factor

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