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

Virieux-Petit, Maxine; Hammer-Dedet, Florence; Aujoulat, Fabien; Jumas‐Bilak, Estelle; Romano-Bertrand, Sara

doi:10.3390/genes13020301

Cited by 27 publications

(21 citation statements)

References 148 publications

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“…P. aeruginosa is qualified as an “Opportunistic Premise Plumbing Pathogen” due to its high capacity to colonize and endure within hospital water networks [ 141 ]. Hence, biofilms present in such environments can be a reservoir of opportunistic strains, including P. aeruginosa [ 142 , 143 ]. This bacterium can survive different water treatments, including sub-chlorination, application of antibiotics and biocides, and thermal shock [ 142 , 144 ].…”

Section: Antibiotic Resistancementioning

confidence: 99%

Mechanisms of Antibiotic and Biocide Resistance That Contribute to Pseudomonas aeruginosa Persistence in the Hospital Environment

Verdial¹,

Serrano

Tavares

et al. 2023

Biomedicines

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Pseudomonas aeruginosa is an opportunistic bacterial pathogen responsible for multiple hospital- and community-acquired infections, both in human and veterinary medicine. P. aeruginosa persistence in clinical settings is worrisome and is a result of its remarkable flexibility and adaptability. This species exhibits several characteristics that allow it to thrive under different environmental conditions, including the ability to colonize inert materials such as medical equipment and hospital surfaces. P. aeruginosa presents several intrinsic mechanisms of defense that allow it to survive external aggressions, but it is also able to develop strategies and evolve into multiple phenotypes to persevere, which include antimicrobial-tolerant strains, persister cells, and biofilms. Currently, these emergent pathogenic strains are a worldwide problem and a major concern. Biocides are frequently used as a complementary/combination strategy to control the dissemination of P. aeruginosa-resistant strains; however, tolerance to commonly used biocides has also already been reported, representing an impediment to the effective elimination of this important pathogen from clinical settings. This review focuses on the characteristics of P. aeruginosa responsible for its persistence in hospital environments, including those associated with its antibiotic and biocide resistance ability.

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Section: Antibiotic Resistancementioning

confidence: 99%

Mechanisms of Antibiotic and Biocide Resistance That Contribute to Pseudomonas aeruginosa Persistence in the Hospital Environment

Verdial¹,

Serrano

Tavares

et al. 2023

Biomedicines

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“…Indeed, copper tolerance (and likely acquisition) plays an important role in the establishment of preinfection communities of P . aeruginosa [ 88 ] and strains defective in copper homeostasis show decreased pathogenicity [ 37 ]. One interesting model that has been recently proposed is that P .…”

Section: Copper Homeostasis In the Gram-negative Periplasm Reflects C...mentioning

confidence: 99%

“…One interesting model that has been recently proposed is that P . aeruginosa is subjected to copper excess and starvation outside of the human body, and that adaptation to copper-related evolutionary pressure increases this bacterium’s ability to adapt to copper fluctuations within the human host [ 88 ].…”

Section: Copper Homeostasis In the Gram-negative Periplasm Reflects C...mentioning

confidence: 99%

Copper microenvironments in the human body define patterns of copper adaptation in pathogenic bacteria

2022

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Copper is an essential micronutrient for most organisms that is required as a cofactor for crucial copper-dependent enzymes encoded by both prokaryotes and eukaryotes. Evidence accumulated over several decades has shown that copper plays important roles in the function of the mammalian immune system. Copper accumulates at sites of infection, including the gastrointestinal and respiratory tracts and in blood and urine, and its antibacterial toxicity is directly leveraged by phagocytic cells to kill pathogens. Copper-deficient animals are more susceptible to infection, whereas those fed copper-rich diets are more resistant. As a result, copper resistance genes are important virulence factors for bacterial pathogens, enabling them to detoxify the copper insult while maintaining copper supply to their essential cuproenzymes. Here, we describe the accumulated evidence for the varied roles of copper in the mammalian response to infections, demonstrating that this metal has numerous direct and indirect effects on immune function. We further illustrate the multifaceted response of pathogenic bacteria to the elevated copper concentrations that they experience when invading the host, describing both conserved and species-specific adaptations to copper toxicity. Together, these observations demonstrate the roles of copper at the host–pathogen interface and illustrate why bacterial copper detoxification systems can be viable targets for the future development of novel antibiotic drug development programs.

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“…The long-term success of these copper-based treatments requires information on the level of copper tolerance, the mechanisms conferring resistance, and its spread through horizontal gene transfer (HGT) not only among nosocomial pathogens but also within bacterial populations in their natural environments. This issue is particularly noteworthy since most opportunistic pathogens acquire multidrug resistance from their nonclinical primary habitat ( Samreen et al, 2021 ; Sanz-García et al, 2021 ; Thummeepak et al, 2020 ; Virieux-Petit et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Five copper homeostasis gene clusters encode the Cu-efflux resistome of the highly copper-tolerant Methylorubrum extorquens AM1

Dávalos¹,

Santos²

2023

PeerJ

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Background In the last decade, the use of copper has reemerged as a potential strategy to limit healthcare-associated infections and to control the spread of multidrug-resistant pathogens. Numerous environmental studies have proposed that most opportunistic pathogens have acquired antimicrobial resistance in their nonclinical primary habitat. Thus, it can be presumed that copper-resistant bacteria inhabiting a primary commensal niche might potentially colonize clinical environments and negatively affect the bactericidal efficacy of Cu-based treatments. The use of copper in agricultural fields is one of the most important sources of Cu pollution that may exert selection pressure for the increase of copper resistance in soil and plant-associated bacteria. To assess the emergence of copper-resistant bacteria in natural habitats, we surveyed a laboratory collection of bacterial strains belonging to the order Rhizobiales. This study proposes that Methylorubrum extorquens AM1 is an environmental isolate well adapted to thrive in copper-rich environments that could act as a reservoir of copper resistance genes. Methods The minimal inhibitory concentrations (MICs) of CuCl2 were used to estimate the copper tolerance of eight plant-associated facultative diazotrophs (PAFD) and five pink-pigmented facultative methylotrophs (PPFM) belonging to the order Rhizobiales presumed to come from nonclinical and nonmetal-polluted natural habitats based on their reported source of isolation. Their sequenced genomes were used to infer the occurrence and diversity of Cu-ATPases and the copper efflux resistome of Mr. extorquens AM1. Results These bacteria exhibited minimal inhibitory concentrations (MICs) of CuCl2 ranging between 0.020 and 1.9 mM. The presence of multiple and quite divergent Cu-ATPases per genome was a prevalent characteristic. The highest copper tolerance exhibited by Mr. extorquens AM1 (highest MIC of 1.9 mM) was similar to that found in the multimetal-resistant model bacterium Cupriavidus metallidurans CH34 and in clinical isolates of Acinetobacter baumannii. The genome-predicted copper efflux resistome of Mr. extorquens AM1 consists of five large (6.7 to 25.7 kb) Cu homeostasis gene clusters, three clusters share genes encoding Cu-ATPases, CusAB transporters, numerous CopZ chaperones, and enzymes involved in DNA transfer and persistence. The high copper tolerance and the presence of a complex Cu efflux resistome suggest the presence of relatively high copper tolerance in environmental isolates of Mr. extorquens.

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

Cited by 27 publications

References 148 publications

Mechanisms of Antibiotic and Biocide Resistance That Contribute to Pseudomonas aeruginosa Persistence in the Hospital Environment

Mechanisms of Antibiotic and Biocide Resistance That Contribute to Pseudomonas aeruginosa Persistence in the Hospital Environment

Copper microenvironments in the human body define patterns of copper adaptation in pathogenic bacteria

Five copper homeostasis gene clusters encode the Cu-efflux resistome of the highly copper-tolerant Methylorubrum extorquens AM1

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