title: Antibiotic-induced replication stress triggers bacterial competence by increasing gene dosage near the origin.
abstract: Streptococcus pneumoniae (pneumococcus) kills nearly 1 million children annually, and the emergence of antibiotic-resistant strains poses a serious threat to human health. Because pneumococci can take up DNA from their environment by a process called competence, genes associated with antibiotic resistance can rapidly spread. Remarkably, competence is activated in response to several antibiotics. Here, we demonstrate that antibiotics targeting DNA replication cause an increase in the copy number of genes proximal to the origin of replication (oriC). As the genes required for competence initiation are located near oriC, competence is thereby activated. Transcriptome analyses show that antibiotics targeting DNA replication also upregulate origin-proximal gene expression in other bacteria. This mechanism is a direct, intrinsic consequence of replication fork stalling. Our data suggest that evolution has conserved the oriC-proximal location of important genes in bacteria to allow for a robust response to replication stress without the need for complex gene-regulatory pathways. PAPERCLIP:
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands.
authors.forename: Jelle
authors.initials: J
authors.lastname: Slager
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands.
authors.forename: Morten
authors.initials: M
authors.lastname: Kjos
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Attaiech
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands. Electronic address: j.w.veening@rug.nl.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Veening
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000235:genetics; D018407:Bacterial Physiological Phenomena; D004261:DNA Replication / Q000187:drug effects*; D061269:DNA Transformation Competence; D018628:Gene Dosage; D015964:Gene Expression Regulation, Bacterial; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D018741:Replication Origin; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D019384:Nucleic Acid Synthesis Inhibitors