Diversity and Role of Prophages in Pseudomonas aeruginosa: Resistance Genes and Bacterial Interactions

<i>Pseudomonas aeruginosa</i> is a major pathogen associated with hospital-acquired infections, and the spread of carbapenem-resistant isolates highlights the urgency of developing non-conventional therapies, such as phage therapy. For this alternative to be effective, understanding phage-host interactions is crucial for the selection of candidate phages and offers new insights into these dynamics. <b>Background/Objectives</b>: This study aimed to characterize prophage diversity in clinical <i>P. aeruginosa</i> genomes, assess the relationship between phages and the CRISPR/Cas system, and investigate the potential role of prophages in disseminating resistance genes. <b>Methods</b>: A total of 141 genomes from Brazilian hospitals were analyzed. Prophage detection was performed using VIBRANT, and in silico analyses were conducted to evaluate taxonomic diversity, the presence of resistance genes, phage life cycle, genomic distribution, and the presence of the CRISPR/Cas system. <b>Results</b>: A total of 841 viral sequences were identified by the VIBRANT tool, of which 498 were confirmed by CheckV, with a predominance of the class Caudoviricetes and high overall phage diversity. No statistically significant difference was observed in the number of prophages between isolates with and without CRISPR/Cas systems. Prophages carrying resistance genes such as <i>rsmA</i>, <i>OXA-56</i>, <i>SPM-1</i>, and others were detected in isolates harboring the type I-C CRISPR/Cas system. Additionally, prophages showed no preference for specific insertion sites along the bacterial genome. <b>Conclusions</b>: These findings provide evidence of a well-established phage-host relationship. The dual role of prophages-as vectors of antimicrobial resistance and as potential therapeutic agents-reflects their dynamic impact on bacterial communities and reinforces their importance in developing new strategies to combat antimicrobial resistance.