In Silico Genomic Analysis of Antibiotic Resistance Genes Carried by Mobile Genetic Elements in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a notable opportunistic pathogen in the ESKAPE group due to its multidrug resistance (MDR) and its ability to cause severe healthcare-associated infections. Horizontal gene transfer (HGT) facilitates the dissemination of antibiotic resistance genes (ARGs) through mobile genetic elements (MGEs). A comprehensive genomic analysis of ARGs associated with these elements is essential to understand multidrug resistance in P. aeruginosa. Here, we analyzed 10,412 publicly available P. aeruginosa genome assemblies defined by the Genome Taxonomy Database (GTDB, release 226) species cluster, which provides standardized prokaryotic genome taxonomy. We identified plasmids, prophages, integrative and conjugative elements (ICEs), and integrative and mobilizable elements (IMEs) carrying ARGs. A group of highly prevalent ARG families was identified in P. aeruginosa, comprising mexD, fosA, catB7, blaPAO, and aph(3′)-IIb, each of which was detected in over 96% of the genome assemblies. In contrast, 313 ARG families were found in fewer than 20% of the genomes. Many ARGs were located on plasmids, with certain pairs co-occurring frequently, such as aph(3″)-Ib and aph(6)-Id, CmlA9 and aadA6, or aac(6′)-Ib3 and aph(3′)-XV, which were associated with specific plasmids. Some of these plasmids closely resembled plasmids from E. coli and K. pneumoniae. Moreover, other MGEs displayed distinct ARG cargo enrichment: mexD on IMEs, aph(3′)-IIb on prophages, and sul1, fosA, and catB7 on ICEs. Our study provides a high-resolution map of the P. aeruginosa MGE resistome and highlights the potential roles of MGEs in disseminating different resistance genes. Our results emphasize the significance of ICE- and plasmid-associated ARG dissemination, particularly sul1, which may be linked to class 1 integrons. They also suggest that interspecies plasmid exchange may contribute to the evolution of MDR in P. aeruginosa.