Diversity and evolution of an abundant ICE clc family of integrative and conjugative elements in Pseudomonas aeruginosa .

Integrative and conjugative elements (ICEs) are widespread autonomous mobile DNA elements, containing the genes necessary for their excision, conjugative transfer, and insertion into a new host cell. ICEs can carry additional genes that are non-essential for their transfer but can confer adaptive phenotypes to the host. Our aim here was to better characterize the presence, distribution, and variation of ICEs related to the well-described ICE clc among Pseudomonas aeruginosa clinical isolates within a geographically restrained environment to understand the factors contributing to their evolution. We examined a total of 181 P . aeruginosa genome sequences obtained from patient or hospital environment isolates, most of which were obtained from a single hospital during 20 years of sampling. More than 90% of the isolates carried one or more ICE clc -like elements, with different degrees of conservation to the known ICE clc lifestyle and transfer genes. ICE clones closely matched their host clonal phylogeny, but not exclusively, indicating that both clonal evolution and ICE horizontal transfer are occurring in the hospital environment. ICEs from this singular hospital environment were mainly associated to three clone types found worldwide, suggesting an enrichment of local clones. Variable gene regions among the clinical P. aeruginosa ICE clc -type elements were notably enriched for heavy metal resistance genes, toxin-anti-toxin systems, potential efflux systems and multidrug resistance proteins, a metalloprotease and for a variety of regulatory systems, but not for specific recognizable antibiotic-resistance cassettes. Clonal persistence suggests adaptive benefits of these functional categories, and micro-patterns of gene gain and loss indicate ongoing ICE evolution within the P. aeruginosa hosts. IMPORTANCE Microbial populations swiftly adapt to changing environments through horizontal gene transfer. While the mechanisms of gene transfer are well known, the impact of environmental conditions on the selection of transferred gene functions remains less clear. We investigated ICEs, specifically the ICE clc -type, in Pseudomonas aeruginosa clinical isolates. Our findings revealed co-evolution between ICEs and their hosts, with ICE transfers occurring within strains. Gene functions carried by ICEs are positively selected, including potential virulence factors and heavy metal resistance. Comparison to publicly available P. aeruginosa genomes unveiled widespread antibiotic-resistance determinants within ICE clc clades. Thus, the ubiquitous ICE clc family significantly contributes to P. aeruginosa 's adaptation and fitness in diverse environments.