Urinary health: focus on the vesical bacteriophages

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Bacteriophages are still under-researched despite their overabundance in human microbiotas. A study has drawn up the first inventory of the lysogenic phages of bladder bacteria and suggests their possible role in urinary health.

 

Phages that infect the bacteria of our microbiotas represent the largest part of the human virome, far ahead of eukaryotic viruses. However, they are still largely under-researched. A North American team has recently addressed this issue by carrying out the first study on the lysogenic phages of vesical bacteria. As a reminder, once present in an infected bacterium, a bacteriophage either enters the lytic phase and kills its host; or enters the lysogenic phase where it can stay as a plasmid in the cytoplasm, incorporate its genome into that of its host, or transition into lytic mode. A change from lysogenic mode to lytic mode in the intestinal microbiota has been associated with diseases.

Specific phages

Using urine from women in good health and from women presenting with lower urinary tract symptoms (cystitis, stress incontinence, overactive bladder), 181 strains representative of the urinary microbiota were isolated and their genome sequenced. In total, 86 % of total bacterial samples displayed at least one prophage sequence (bacteriophage genome), for the most part not identified at this time. Lactobacilli hosted more than one prophage, the L. jensenii strain UMB0077 having the largest number of these (10). Aside from a few Lactobacillus prophage sequences which displayed some homology with the vaginal Lactobacillus Lv1 prophage, the sequences identified did not resemble any sequence of the lysogenic or lytic vaginal phages currently known, suggesting the existence of subpopulations specific to each of the two microbiotas.

Numerous target species

The team also identified 129 new phages in the Actinomycetes, Varibaculum, Bifidobacterium, Gardnerella, and Streptococcus species and the uropathogenic bacterium Proteus mirabilis, which to date have not been described, highlighting the richness of this currently uncharacterized bacteriophage diversity. This observation is not specific to the vesical virome: around 50% of intestinal virome phages have not been classified. While some phage sequences are linked to a single bacterial host, others seem to be associated with several bacterial hosts simultaneously, suggesting that some phages could target several bacterial species. This broad host range concept is controversial, say the authors. But this property could allow phages to infect a new bacterium when its original host is the target of treatment.

A role which remains to be defined

Like the intestinal or vaginal microbiome, the hypothesis of a functional core population of phages in the bladder would be plausible based on the abundance of lysogenic phages and the similarity of sequences in all samples. Certain phages specific to Actinomycetaceae have been found only in women with overactive bladder. Although non-significant, these variations between patients and healthy subjects could suggest a role for bacteriophages in urinary health or its symptoms. Phages could therefore be involved in the stability of the urinary microbiota, as has been demonstrated for intestinal microbiota. Other studies suggest that Lactobacillus phages could play a role in microbiota dysbiosis in the vagina and contribute to bacterial vaginosis. However, no harmful effect on the urinary microbiota was observed in this study. Bacteriophages thus introduce a new level of complexity into the understanding of our microbiota, and a potentially fruitful avenue of research.

 

Sources:

T Miller-Ensminger et al. Bacteriophages of the urinary microbiome. J Bacteriol. 2018; Jan 29