Bacteriophages and diffusion of genes encoding antimicrobial resistance in cystic fibrosis sputum microbiota.

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.
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