The hospital environment constitutes a reservoir of opportunistic pathogens responsible for healthcare-associated infections (HCAI) such as Pseudomonas aeruginosa (Pa). Pa persistence within technological niches, the increasing emergence of epidemic high-risk clones in HCAI, the epidemiological link between plumbing strains and clinical strains, make it a major nosocomial pathogen. Therefore, understanding the mechanisms of Pa adaptation to hospital water systems would be useful in preventing HCAI. This review deciphers how copper resistance contributes to Pa adaptation and persistence in a hospital environment, especially within copper water systems, and ultimately to its success as a causative agent of HCAI. Numerous factors are involved in copper homeostasis in Pa, among which active efflux conferring copper tolerance, and copper-binding proteins regulating the copper compartmentalization between periplasm and cytoplasm. The functional harmony of copper homeostasis is regulated by several transcriptional regulators. The genomic island GI-7 appeared as especially responsible for the copper resistance in Pa. Mechanisms of copper and antibiotic cross-resistance and co-resistance are also identified, with potential co-regulation processes between them. Finally, copper resistance of Pa confers selective advantages in colonizing and persisting in hospital environments but also appears as an asset at the host/pathogen interface that helps in HCAI occurrence.

Background. Descriptions of genomic characters and dynamics related to Pseudomonas aeruginosa (PA) adaptation and survival in hospital water networks remain scarce but necessary for sustainable water management in hospitals. Methods. A new copper water network in an intensive care unit (ICU) was chronically colonized by a genotype sequence type (ST) 299 of PA and sporadically by a genotype ST2685. Sixty-eight ST299-PA and four ST2685-PA strains from ICU-water samples collected over 29 months and 4 months, respectively, were studied for genomic adaptation to copper water network. PFGE and whole-genome sequencing allowing SNP, comparative genomics, resistome, virulome and pangenome analyses were performed. In order to understand the adaptive phenomena linked to the colonization niche, 16 isolates of ST299-PA colonizing a cystic fibrosis (CF) patient during 16 months were included. Results and discussion. The 68 ST299-PA ICU-water differed by <0.15 SNPs on average. No recombination regions nor patho-adaptive mutations were identified. Resistome, virulome and pangenome were stable over the time. The genomic content included a copper resistance operon, mainly metal resistance genes, a Tn 4661 -like transposon, the class 1 integron and broad-spectrum efflux pumps. These elements, absent in ST2685-PA ICU-water, support the survival of ST299-PA in the copper water network. The evolutionary speed of ST299-PA CF was faster with 12.9 SNPs among strains mostly affecting genes of patho-adaptation, arguing that the primo-colonization strain was probably not adapted to the niche, in contrast to the high genomic stability observed for the ST299-PA ICU-water population signifying the primary adaptation to the water network.