title: The agr locus regulates virulence and colonization genes in Clostridium difficile 027.
abstract: The transcriptional regulator AgrA, a member of the LytTR family of proteins, plays a key role in controlling gene expression in some Gram-positive pathogens, including Staphylococcus aureus and Enterococcus faecalis. AgrA is encoded by the agrACDB global regulatory locus, and orthologues are found within the genome of most Clostridium difficile isolates, including the epidemic lineage 027/BI/NAP1. Comparative RNA sequencing of the wild type and otherwise isogenic agrA null mutant derivatives of C. difficile R20291 revealed a network of approximately 75 differentially regulated transcripts at late exponential growth phase, including many genes associated with flagellar assembly and function, such as the major structural subunit, FliC. Other differentially regulated genes include several involved in bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) synthesis and toxin A expression. C. difficile 027 R20291 agrA mutant derivatives were poorly flagellated and exhibited reduced levels of colonization and relapses in the murine infection model. Thus, the agr locus likely plays a contributory role in the fitness and virulence potential of C. difficile strains in the 027/BI/NAP1 lineage.
authors.affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, University of London, London, United Kingdom.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Martin
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.forename: Alexandra
authors.initials: A
authors.lastname: Faulds-Pain
authors.forename: Lars
authors.initials: L
authors.lastname: Barquist
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Browne
authors.forename: Laura
authors.initials: L
authors.lastname: Pettit
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Lawley
authors.forename: Brendan W
authors.initials: BW
authors.lastname: Wren
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002874:Chromosome Mapping; D002876:Chromosomes, Bacterial; D016360:Clostridioides difficile / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D016680:Genome, Bacterial; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D018085:Regulon; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial