Abstract
Pseudmonas aeruginosa is a Gram-negative bacterium known to be ubiquitous and recognized as one of the leading causes of infections such as respiratory, urinary tract, burns, cystic fibrosis, and in immunocompromised individuals. Failure of antimicrobial therapy has been documented to be attributable due to the development of various resistance mechanisms, with a proclivity to develop additional resistance mechanisms rapidly. P. aeruginosa virulence attenuation is an alternate technique for disrupting pathogenesis without impacting growth. The iron-scavenging siderophores (pyoverdine and pyochelin) generated by P. aeruginosa have various properties like scavenging iron, biofilm formation, quorum sensing, increasing virulence, and toxicity to the host. As a result, develo** an antivirulence strategy, specifically inhibiting the P. aeruginosa siderophore, has been a promising therapeutic option to limit their infection. Several natural, synthetic compounds and nanoparticles have been identified as potent inhibitors of siderophore production/biosynthesis, function, and transport system. The current review discussed pyoverdine and pyochelin’s synthesis and transport system in P. aeruginosa. Furthermore, it is also focused on the role of several natural and synthetic compounds in reducing P. aeruginosa virulence by inhibiting siderophore synthesis, function, and transport. The underlying mechanism involved in inhibiting the siderophore by natural and synthetic compounds has also been explained.
Key points
• Pseudomonas aeruginosa is an opportunistic pathogen linked to chronic respiratory, urinary tract, and burns infections, as well as cystic fibrosis and immunocompromised patients.
• P. aeruginosa produces two virulent siderophores forms: pyoverdine and pyochelin, which help it to survive in iron-deficient environments.
• The inhibition of siderophore production, transport, and activity using natural and synthesized drugs has been described as a potential strategy for controlling P. aeruginosa infection.
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(Reproduced with permission from reference (Khan et al. 2021), Copyright 2021 by the authors and licensee MDPI, Basel, Switzerland), and D inhibition of pyoverdine by gold nanoparticles and zinc oxide nanoparticles synthesized from Leuconostoc sp. strain C2 (reproduced with permission from reference (Kang et al. 2022), Copyright 2022 by the authors and licensee MDPI, Basel, Switzerland)
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This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education (2021R1A6A1A03039211 and 2022R1A2B5B01001998).
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GJJ collected data, wrote, and reviewed the manuscript; FK conceptualized the idea, collected the literature, drafted, and reviewed the manuscript; SK collected the data and wrote the manuscript; NT collected data and wrote the manuscript; SM collected the data and wrote the manuscript, and YMK supervision, funding, writing, and editing. All authors read and approved the manuscript.
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Jeong, GJ., Khan, F., Khan, S. et al. Pseudomonas aeruginosa virulence attenuation by inhibiting siderophore functions. Appl Microbiol Biotechnol 107, 1019–1038 (2023). https://doi.org/10.1007/s00253-022-12347-6
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DOI: https://doi.org/10.1007/s00253-022-12347-6