Abstract
BACKGROUND: Clostridium difficile is an anaerobic, Gram-positive bacterium that can reside as a commensal within the intestinal microbiota of healthy individuals or cause life-threatening antibiotic-associated diarrhea in immunocompromised hosts. C. difficile can also form highly resistant spores that are excreted facilitating host-to-host transmission. The C. difficile spo0A gene encodes a highly conserved transcriptional regulator of sporulation that is required for relapsing disease and transmission in mice.
RESULTS: Here we describe a genome-wide approach using a combined transcriptomic and proteomic analysis to identify Spo0A regulated genes. Our results validate Spo0A as a positive regulator of putative and novel sporulation genes as well as components of the mature spore proteome. We also show that Spo0A regulates a number of virulence-associated factors such as flagella and metabolic pathways including glucose fermentation leading to butyrate production.
CONCLUSIONS: The C. difficile spo0A gene is a global transcriptional regulator that controls diverse sporulation, virulence and metabolic phenotypes coordinating pathogen adaptation to a wide range of host interactions. Additionally, the rich breadth of functional data allowed us to significantly update the annotation of the C. difficile 630 reference genome which will facilitate basic and applied research on this emerging pathogen.
| Original language | English |
|---|---|
| Article number | 160 |
| Number of pages | 15 |
| Journal | BMC Genomics |
| Volume | 15 |
| DOIs | |
| Publication status | Published - 25 Feb 2014 |
Bibliographical note
This project was funded by the Wellcome Trust (grants 098051 and 086418) and a Medical Research Council New Investigator Research Grant (TDL; grant 93614). HJF and SHD receive support from the Scottish Government Food, Land and People programme. WKS was supported by a Gisela Thier Fellowship and a VENI fellowship of the Netherlands Organisation for Scientific Research (NWO-ZonMW).
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- Functional genomics
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