Clostridioides (formerly Clostridium) difficile produces two major toxins, TcdA and TcdB, upon entry into stationary phase. Transcription of tcdA and tcdB requires the specialized sigma factor, σTcdR , which also directs RNA Polymerase to transcribe tcdR itself. We fused a gene for a red fluorescent protein to the tcdA promoter to study toxin gene expression at the level of individual C. difficile cells. Surprisingly, only a subset of cells became red fluorescent upon entry into stationary phase. Breaking the positive feedback loop that controls σTcdR production by engineering cells to express tcdR from a tetracycline-inducible promoter resulted in uniform fluorescence across the population. Experiments with two regulators of tcdR expression, σD and CodY, revealed neither is required for bimodal toxin gene expression. However, σD biased cells towards the Toxin-ON state, while CodY biased cells towards the Toxin-OFF state. Finally, toxin gene expression was observed in sporulating cells. We conclude that (i) toxin production is regulated by a bistable switch governed by σTcdR , which only accumulates to high enough levels to trigger toxin gene expression in a subset of cells, and (ii) toxin production and sporulation are not mutually exclusive developmental programs. This article is protected by copyright. All rights reserved.
Pharmacology, Toxicology and Pharmaceutical Science
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2%
Other
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Unknown
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 August 2018.
All research outputs
#7,804,362
of 27,879,744 outputs
Outputs from Molecular Microbiology
#2,746
of 7,358 outputs
Outputs of similar age
#117,279
of 362,400 outputs
Outputs of similar age from Molecular Microbiology
#43
of 116 outputs
Altmetric has tracked 27,879,744 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 7,358 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has gotten more attention than average, scoring higher than 62% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 362,400 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
We're also able to compare this research output to 116 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 62% of its contemporaries.
