title: The master activator of IncA/C conjugative plasmids stimulates genomic islands and multidrug resistance dissemination.
abstract: Dissemination of antibiotic resistance genes occurs mostly by conjugation, which mediates DNA transfer between cells in direct contact. Conjugative plasmids of the IncA/C incompatibility group have become a substantial threat due to their broad host-range, the extended spectrum of antimicrobial resistance they confer, their prevalence in enteric bacteria and their very efficient spread by conjugation. However, their biology remains largely unexplored. Using the IncA/C conjugative plasmid pVCR94ΔX as a prototype, we have investigated the regulatory circuitry that governs IncA/C plasmids dissemination and found that the transcriptional activator complex AcaCD is essential for the expression of plasmid transfer genes. Using chromatin immunoprecipitation coupled with exonuclease digestion (ChIP-exo) and RNA sequencing (RNA-seq) approaches, we have identified the sequences recognized by AcaCD and characterized the AcaCD regulon. Data mining using the DNA motif recognized by AcaCD revealed potential AcaCD-binding sites upstream of genes involved in the intracellular mobility functions (recombination directionality factor and mobilization genes) in two widespread classes of genomic islands (GIs) phylogenetically unrelated to IncA/C plasmids. The first class, SGI1, confers and propagates multidrug resistance in Salmonella enterica and Proteus mirabilis, whereas MGIVmi1 in Vibrio mimicus belongs to a previously uncharacterized class of GIs. We have demonstrated that through expression of AcaCD, IncA/C plasmids specifically trigger the excision and mobilization of the GIs at high frequencies. This study provides new evidence of the considerable impact of IncA/C plasmids on bacterial genome plasticity through their own mobility and the mobilization of genomic islands.
authors.affiliation: Laboratory of bacterial molecular genetics, Département de biologie, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Carraro
authors.affiliation: Laboratory of microbial systems and synthetic biology, Département de biologie, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Dominick
authors.initials: D
authors.lastname: Matteau
authors.affiliation: Laboratory of bacterial molecular genetics, Département de biologie, Université de Sherbrooke, Sherbrooke, Canada; CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Luo
authors.affiliation: Laboratory of microbial systems and synthetic biology, Département de biologie, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Rodrigue
authors.affiliation: Laboratory of bacterial molecular genetics, Département de biologie, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Burrus
mesh_terms: D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D016680:Genome, Bacterial; D044404:Genomic Islands / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D010957:Plasmids / Q000235:genetics*; D011513:Proteus mirabilis / Q000235:genetics; D019779:Salmonella enterica / Q000235:genetics