title: Bacteriophages and diffusion of genes encoding antimicrobial resistance in cystic fibrosis sputum microbiota.
abstract: OBJECTIVE
  The cystic fibrosis (CF) airway is now considered the site of a complex microbiota, where cross-talking between microbes and lateral gene transfer are believed to contribute to the adaptation of bacteria to this specific environment and to the emergence of multidrug-resistant bacteria. The objective of this study was to retrieve and analyse specific sequences associated with antimicrobial resistance from the CF viromes database.
  
  
  METHODS
  Specific sequences from CF metagenomic studies related to the 'antibiotic and toxic compound resistance' dataset were retrieved from the MG-RAST web site, assembled and functionally annotated for identification of the genes. Phylogenetic trees were constructed using a minimum parsimony starting tree topology search strategy.
  
  
  RESULTS
  Overall, we found 1031 short sequences in the CF virome putatively encoding resistance to antimicrobials versus only 3 reads in the non-CF virome dataset (P = 0.001). Among them, we could confidently identify 66 efflux pump genes, 15 fluoroquinolone resistance genes and 9 β-lactamase genes. Evolutionary relatedness determined using phylogenetic information demonstrates the different origins of these genes among the CF microbiota. Interestingly, among annotated sequences within CF viromes, we also found matching 16S rDNA sequences from Escherichia, Cyanobacteria and Bacteroidetes.
  
  
  CONCLUSIONS
  Our results suggest that phages in the CF sputum microbiota represent a reservoir of mobilizable genes associated with antimicrobial resistance that may spread in this specific niche. This phenomenon could explain the fantastic adaptation of CF strains to their niche and may represent a new potential therapeutic target to prevent the emergence of multidrug-resistant bacteria, which are responsible for most of the deaths in CF.
authors.affiliation: URMITE UMR CNRS-IRD 6236, IFR48, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Fancello
authors.forename: Christelle
authors.initials: C
authors.lastname: Desnues
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Rolain
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001435:Bacteriophages / Q000235:genetics*; D041963:Bacteroidetes / Q000187:drug effects / Q000235:genetics; D000458:Cyanobacteria / Q000187:drug effects / Q000235:genetics; D003550:Cystic Fibrosis / Q000382:microbiology* / Q000821:virology*; D004275:DNA, Ribosomal / Q000302:isolation & purification; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004925:Escherichia / Q000187:drug effects / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology; D022761:Gene Transfer, Horizontal; D054892:Metagenome; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000302:isolation & purification; D013183:Sputum / Q000382:microbiology / Q000821:virology; D001618:beta-Lactamases / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004275:DNA, Ribosomal; D024841:Fluoroquinolones; D012336:RNA, Ribosomal, 16S; D001618:beta-Lactamases