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.2018 Mar 12;200(7):e00738-17.
doi: 10.1128/JB.00738-17. Print 2018 Apr 1.

Bacteriophages of the Urinary Microbiome

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Bacteriophages of the Urinary Microbiome

Taylor Miller-Ensminger et al. J Bacteriol..

Abstract

Bacterial viruses (bacteriophages) play a significant role in microbial community dynamics. Within the human gastrointestinal tract, for instance, associations among bacteriophages (phages), microbiota stability, and human health have been discovered. In contrast to the gastrointestinal tract, the phages associated with the urinary microbiota are largely unknown. Preliminary metagenomic surveys of the urinary virome indicate a rich diversity of novel lytic phage sequences at an abundance far outnumbering that of eukaryotic viruses. These surveys, however, exclude the lysogenic phages residing within the bacteria of the bladder. To characterize this phage population, we examined 181 genomes representative of the phylogenetic diversity of bacterial species within the female urinary microbiota and found 457 phage sequences, 226 of which were predicted with high confidence. Phages were prevalent within the bladder bacteria: 86% of the genomes examined contained at least one phage sequence. Most of these phages are novel, exhibiting no discernible sequence homology to sequences in public data repositories. The presence of phages with substantial sequence similarity within the microbiota of different women supports the existence of a core community of phages within the bladder. Furthermore, the observed variation between the phage populations of women with and without overactive bladder symptoms suggests that phages may contribute to urinary health. To complement our bioinformatic analyses, viable phages were cultivated from the bacterial isolates for characterization; a novel coliphage was isolated, which is obligately lytic in the laboratory strainEscherichia coli C. Sequencing of bacterial genomes facilitates a comprehensive cataloguing of the urinary virome and reveals phage-host interactions.IMPORTANCE Bacteriophages are abundant within the human body. However, while some niches have been well surveyed, the phage population within the urinary microbiome is largely unknown. Our study is the first survey of the lysogenic phage population within the urinary microbiota. Most notably, the abundance of prophage exceeds that of the bacteria. Furthermore, many of the prophage sequences identified exhibited no recognizable sequence homology to sequences in data repositories. This suggests a rich diversity of uncharacterized phage species present in the bladder. Additionally, we observed a variation in the abundances of phages between bacteria isolated from asymptomatic "healthy" individuals and those with urinary symptoms, thus suggesting that, like phages within the gut, phages within the bladder may contribute to urinary health.

Keywords: bacteria; bacteriophages; microbiome; prophage; urinary tract; virus.

Copyright © 2018 American Society for Microbiology.

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Figures

FIG 1
FIG 1
Phage presence within bacteria of the bladder. Each phage sequence identified at a high confidence is represented by a dot on the isolate's branch in the phylogenetic tree, which was built using the 16S rRNA gene sequences of the isolates. The phyla for the isolates in the phylogenetic tree are indicated in the outer circle, with “B” indicating the single isolate from the phylum Bacteroidetes. Red and blue circles represent unintegrated phages of categories 1 and 2, respectively. Green and yellow circles represent integrated phages of categories 4 and 5, respectively. It is important to note that branches without dots may include lower-quality predictions (categories 3 and 6).
FIG 2
FIG 2
Phage conserved among Actinomycetaceae strains isolated from different patients. Syntenic regions are shown between the strains. The annotations for coding regions within each syntenic block are listed in the corresponding colors. ECF, energy-coupling factor.
FIG 3
FIG 3
Average number of high-confidence phage sequences per genome isolated from control and OAB patients. Genera with representatives from both patient populations are shown.
FIG 4
FIG 4
TEM of phage isolated from bladder strain E. coli UMB0901.
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