Abstract
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.
Highlights
Pseudomonas aeruginosa (Pa) is characterized by a broad capacity to colonize and persist within hospital environments [3] especially in wet technological niches such as plumbing networks where it is qualified as Opportunistic Premise Plumbing Pathogen (OPPP) [4]
This adaptation to the hospital environment and success in healthcare-associated infections (HCAI) is conferred by its ability to form biofilms, its metabolic versatility, and its strong resistance to antimicrobial agents marked by the emergence of Multi-Drug Resistant (MDR) or eXtremly-Drug
Compartmentalization of Copper Requirements: A Dynamic between the Cytoplasmic and According to Parmar et al [60], when Pa is confronted with external copper concentrations around 1mM, the periplasmic copper pool becomes larger than the cytoplasmic pool
Summary
The opportunistic pathogen, P. aeruginosa (Pa) is a major causative agent of healthcareassociated infections (HCAI) [1,2]. It is interesting to keep in mind that some EHRs, such as ST308 or ST395 isolates, for example, can respond to both wild-type and MDR profiles [20] This suggests that an essential characteristic of EHR clones, beyond their major capacity to resist antibiotics, would be the ability to acquire antimicrobial resistance determinants in case of high pressure or virulence traits facilitating their survival, establishment, and their dissemination in the hospital environment. The cytosolic and periplasmic organisation of copper management in Pa to demonstrate the central role of copper tolerance and resistance in its survival in plumbing systems, its involvement in the co-selection of metal and antibiotic resistances and its success as a causative agent of HCAIs. Within the bacterial kingdom, copper is an essential trace element used as a cofactor in various proteins (mainly enzymes such as redox enzymes) [32] because of its redox potential. It can be hypothesised that these genes facilitate the adaptation and survival of Pa in copper-rich environments such as copper water systems
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