title: Transfer activation of SXT/R391 integrative and conjugative elements: unraveling the SetCD regulon.
abstract: Integrative and conjugative elements (ICEs) of the SXT/R391 family have been recognized as key drivers of antibiotic resistance dissemination in the seventh-pandemic lineage of Vibrio cholerae. SXT/R391 ICEs propagate by conjugation and integrate site-specifically into the chromosome of a wide range of environmental and clinical Gammaproteobacteria. SXT/R391 ICEs bear setC and setD, two conserved genes coding for a transcriptional activator complex that is essential for activation of conjugative transfer. We used chromatin immunoprecipitation coupled with exonuclease digestion (ChIP-exo) and RNA sequencing (RNA-seq) to characterize the SetCD regulon of three representative members of the SXT/R391 family. We also identified the DNA sequences bound by SetCD in MGIVflInd1, a mobilizable genomic island phylogenetically unrelated to SXT/R391 ICEs that hijacks the conjugative machinery of these ICEs to drive its own transfer. SetCD was found to bind a 19-bp sequence that is consistently located near the promoter -35 element of SetCD-activated genes, a position typical of class II transcriptional activators. Furthermore, we refined our understanding of the regulation of excision from and integration into the chromosome for SXT/R391 ICEs and demonstrated that de novo expression of SetCD is crucial to allow integration of the incoming ICE DNA into a naive host following conjugative transfer.
authors: Laboratory of Bacterial Molecular Genetics, Département de biologie, Université de Sherbrooke, Sherbrooke, QC, J1K 2R1, Canada.
authors: Dominic
authors: D
authors: Poulin-Laprade
authors: Laboratory of Microbial Systems and Synthetic Biology, Département de biologie, Université de Sherbrooke, Sherbrooke, QC, J1K 2R1, Canada.
authors: Dominick
authors: D
authors: Matteau
authors: Laboratory of Bioinformatics and Genomics, Département de biologie, Université de Sherbrooke, Sherbrooke, QC, J1K 2R1, Canada.
authors: Pierre-Étienne
authors: PÉ
authors: Jacques
authors: Laboratory of Microbial Systems and Synthetic Biology, Département de biologie, Université de Sherbrooke, Sherbrooke, QC, J1K 2R1, Canada Sebastien.Rodrigue@USherbrooke.ca.
authors: Sébastien
authors: S
authors: Rodrigue
authors: Laboratory of Bacterial Molecular Genetics, Département de biologie, Université de Sherbrooke, Sherbrooke, QC, J1K 2R1, Canada Vincent.Burrus@USherbrooke.ca.
authors: Vincent
authors: V
authors: Burrus
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003227:Conjugation, Genetic; D004269:DNA, Bacterial / Q000737:chemistry / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands; D009154:Mutation; D059372:Nucleotide Motifs; D009875:Operator Regions, Genetic; D011401:Promoter Regions, Genetic; D018085:Regulon; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D015534:Trans-Activators