From Copper Tolerance to Resistance in Pseudomonas aeruginosa towards Patho-Adaptation and Hospital Success

Abstract

The hospital environment constitutes a reservoir of opportunistic pathogens responsible for healthcare-associated infections (HCAI) such as <i>Pseudomonas aeruginosa</i> (<i>Pa</i>). <i>Pa</i> 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 <i>Pa</i> adaptation to hospital water systems would be useful in preventing HCAI. This review deciphers how copper resistance contributes to <i>Pa</i> 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 <i>Pa</i>, 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 <i>Pa</i>. Mechanisms of copper and antibiotic cross-resistance and co-resistance are also identified, with potential co-regulation processes between them. Finally, copper resistance of <i>Pa</i> 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.