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Crystal structure and DNA binding activity of a PadR family transcription regulator from hypervirulent Clostridium difficile R20291

Overview of attention for article published in BMC Microbiology, October 2016
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Title
Crystal structure and DNA binding activity of a PadR family transcription regulator from hypervirulent Clostridium difficile R20291
Published in
BMC Microbiology, October 2016
DOI 10.1186/s12866-016-0850-0
Pubmed ID
Authors

Catherine E. Isom, Smita K. Menon, Leonard M. Thomas, Ann H. West, George B. Richter-Addo, Elizabeth A. Karr

Abstract

Clostridium difficile is a spore-forming obligate anaerobe that can remain viable for extended periods, even in the presence of antibiotics, which contributes to the persistence of this bacterium as a human pathogen during host-to-host transmission and in hospital environments. We examined the structure and function of a gene product with the locus tag CDR20291_0991 (cdPadR1) as part of our broader goal aimed at elucidating transcription regulatory mechanisms involved in virulence and antibiotic resistance of the recently emergent hypervirulent C. difficile strain R20291. cdPadR1 is genomically positioned near genes that are involved in stress response and virulence. In addition, it was previously reported that cdPadR1 and a homologue from the historical C. difficile strain 630 (CD630_1154) were differentially expressed when exposed to stressors, including antibiotics. The crystal structure of cdPadR1 was determined to 1.9 Å resolution, which revealed that it belongs to the PadR-s2 subfamily of PadR transcriptional regulators. cdPadR1 binds its own promoter and other promoter regions from within the C. difficile R20291 genome. DNA binding experiments demonstrated that cdPadR1 binds a region comprised of inverted repeats and an AT-rich core with the predicted specific binding motif, GTACTAT(N2)ATTATA(N)AGTA, within its own promoter that is also present in 200 other regions in the C. difficile R20291 genome. Mutation of the highly conserved W in α4 of the effector binding/oligomerization domain, which is predicted to be involved in multi-drug recognition and dimerization in other PadR-s2 proteins, resulted in alterations of cdPadR1 binding to the predicted binding motif, potentially due to loss of higher order oligomerization. Our results indicate that cdPadR1 binds a region within its own promoter consisting of the binding motif GTACTAT(N2)ATTATA(N)AGTA and seems to associate non-specifically with longer DNA fragments in vitro, which may facilitate promoter and motif searching. This suggests that cdPadR1 acts as a transcriptional auto-regulator, binding specific sites within its own promoter, and is part of a broad gene regulatory network involved, in part, with environmental stress response, antibiotic resistance and virulence.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 42 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 14%
Student > Ph. D. Student 6 14%
Student > Master 5 12%
Student > Bachelor 4 10%
Unspecified 3 7%
Other 9 21%
Unknown 9 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 31%
Agricultural and Biological Sciences 5 12%
Unspecified 3 7%
Immunology and Microbiology 3 7%
Chemistry 3 7%
Other 4 10%
Unknown 11 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 06 October 2016.
All research outputs
#20,344,065
of 22,890,496 outputs
Outputs from BMC Microbiology
#2,695
of 3,197 outputs
Outputs of similar age
#276,841
of 319,862 outputs
Outputs of similar age from BMC Microbiology
#59
of 75 outputs
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So far Altmetric has tracked 3,197 research outputs from this source. They receive a mean Attention Score of 4.1. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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