Genomic location of the major ribosomal protein gene locus determines Vibrio cholerae global growth and infectivity

PLoS Genet. 2015 Apr 13;11(4):e1005156. doi: 10.1371/journal.pgen.1005156. eCollection 2015 Apr.

Abstract

The effects on cell physiology of gene order within the bacterial chromosome are poorly understood. In silico approaches have shown that genes involved in transcription and translation processes, in particular ribosomal protein (RP) genes, localize near the replication origin (oriC) in fast-growing bacteria suggesting that such a positional bias is an evolutionarily conserved growth-optimization strategy. Such genomic localization could either provide a higher dosage of these genes during fast growth or facilitate the assembly of ribosomes and transcription foci by keeping physically close the many components of these macromolecular machines. To explore this, we used novel recombineering tools to create a set of Vibrio cholerae strains in which S10-spec-α (S10), a locus bearing half of the ribosomal protein genes, was systematically relocated to alternative genomic positions. We show that the relative distance of S10 to the origin of replication tightly correlated with a reduction of S10 dosage, mRNA abundance and growth rate within these otherwise isogenic strains. Furthermore, this was accompanied by a significant reduction in the host-invasion capacity in Drosophila melanogaster. Both phenotypes were rescued in strains bearing two S10 copies highly distal to oriC, demonstrating that replication-dependent gene dosage reduction is the main mechanism behind these alterations. Hence, S10 positioning connects genome structure to cell physiology in Vibrio cholerae. Our results show experimentally for the first time that genomic positioning of genes involved in the flux of genetic information conditions global growth control and hence bacterial physiology and potentially its evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Drosophila melanogaster / microbiology
  • Gene Dosage
  • Gene Order*
  • Genetic Loci
  • Genome, Bacterial*
  • Ribosomal Proteins / genetics*
  • Vibrio cholerae / genetics
  • Vibrio cholerae / pathogenicity*
  • Virulence / genetics

Substances

  • Bacterial Proteins
  • Ribosomal Proteins

Grant support

This study was supported by ANR-10-BLAN-131301 from French National Research Agency (to DM) and LabEx IBEID (to MCS). ASB was supported by EMBO-ALTF-1473-2010 and Marie Skłodowska-Curie Actions (FP7-PEOPLE-2011-IIF-BMC). JAM is an AXA Fellow. MJB was supported by Pasteur-Paris University (PPU) Program. MEV is an Institut National de la Santé et de la Recherche Médicale (INSERM) researcher. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.