Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy

Despite much promise in overcoming drug-resistant infections, clinical studies of bacteriophage antibacterial therapy have failed to show durable effectiveness. Although lysogeny plays an important role in bacterial physiology, its significance in diverse microbiomes remains unclear. Here, we tested the following hypotheses: 1) urinary microbiome phage populations switch to a higher relative proportion of temperate phages, and 2) the activity of the phage recombination machinery (integration/excision/transposition) is higher during human urinary tract infections (UTIs) than in non-infected urinary tracts. Using human urine, model organisms, mass spectrometry, gene expression analysis, and the phage phenotype prediction model BACPHLIP, the results corroborated our hypotheses at the functional protein and gene levels. From a human health perspective, these data suggest that temperate phages may facilitate bacterial infections rather than function as protective agents. These findings support the use of lysogenic phages as therapeutic Trojan Horses.