Prophages are Infrequently Associated With Antibiotic Resistance in Pseudomonas aeruginosa Clinical Isolates

Antimicrobial resistance (AMR) is a significant obstacle to the treatment of bacterial infections, including in the context of Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF). Lysogenic bacteriophages can integrate their genome into the bacterial chromosome and are known to promote genetic transfer between bacterial strains. However, the contribution of lysogenic phages to the incidence of AMR is poorly understood. Here, in a set of 187 clinical isolates of Pseudomonas aeruginosa collected from 82 patients with CF, we evaluate the links between prophages and both genomic and phenotypic resistance to five anti-pseudomonal antibiotics: tobramycin, colistin, ciprofloxacin, meropenem, aztreonam, and tazobactam. We find that P. aeruginosa isolates contain on average 3.06 +/-1.84 (SD) predicted prophages. We find no significant association between the number of prophages per isolate and the mean inhibitory concentration (MIC) for any of these antibiotics. We then investigate the relationship between particular prophages and AMR. We identify a single lysogenic phage that is associated with phenotypic resistance to the antibiotic tobramycin. Consistent with this association, we identify AMR genes associated with resistance to tobramycin in these strains and find that they are not encoded directly on prophage sequences. These findings suggest that prophages are infrequently associated with the AMR genes in clinical isolates of P. aeruginosa .