Abstract
BackgroundClostridium 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.ResultsHere 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.ConclusionsThe 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.
Highlights
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
Our analysis demonstrates that the C. difficile spo0A gene encodes a global transcriptional regulator that coordinates an array of phenotypes associated with host colonization and transmission
C. difficile growth dynamics in vitro We and others [14,15,23] have previously demonstrated that C. difficile 630Δerm produces spores and that an isogenic spo0A::ermB mutant does not, but that sporulation can be restored by expressing the spo0A gene in trans [23]
Summary
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. The C. difficile spo0A gene encodes a highly conserved transcriptional regulator of sporulation that is required for relapsing disease and transmission in mice. Clostridium difficile has emerged over the past decade to become the most common cause of infectious antibioticassociated diarrhea within healthcare systems worldwide [1]. This Gram-positive, anaerobic bacterium commonly resides asymptomatically in healthy individuals who can serve as a transmission reservoir within a hospital setting [2]. C. difficile Spo0A binds directly to DNA upstream of several early sporulation genes [21] but this transcriptional regulator may control other processes not obviously associated with sporulation. In C. difficile Spo0A has been implicated in controlling toxin gene expression [22] and disease in mice [15,23] and biofilm formation in vitro [24,25]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call