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Background <p>Difficult-to-treat resistant (DTR) <i>Pseudomonas aeruginosa</i> has strong drug resistance and can tolerate a diversity of antibiotics. Infections triggered by DTR <i>P. aeruginosa</i> urgently require research and development of innovative antibiotics. β-Carotene is a carotenoid pigment with multiple activities, such as antibacterial, antifungal, antioxidant, and anticancer activities, therefore, the current study aimed to investigate the potential antipseudomonal activity of β-carotene against DTR <i>P. aeruginosa</i> to find a new treatment option.</p> Methods <p>Antimicrobial susceptibility tests were conducted for 100 <i>P. aeruginosa</i> isolates. Well diffusion and broth microdilution techniques were utilized to determine the antibacterial activity of β-carotene. A total of 10 virulence factors (biofilm, pyocyanin, motility, protease, gelatinase, exopolysaccharide, siderophore, hemolysin, pyomelanin, and rhamnolipid) were screened among the tested isolates, and the effect of β-carotene on these virulence factors was assessed. Light microscopy and confocal laser scanning microscopy approaches were established to investigate the effect of β-carotene on biofilm formation by DTR isolates. Molecular analysis, docking study, and the wound infection model further evaluated the antipseudomonal action of β-carotene against DTR isolates.</p> Results <p>All tested multidrug-resistant (MDR) and DTR isolates (<i>n</i> = 40) were susceptible to β-carotene (200&#xa0;µg/ml), with inhibition zones ranging from 10 to 33&#xa0;mm, recording minimum inhibitory concentration (MIC) values of 12.5 to 100&#xa0;µg/ml. It was reported that β-carotene reduced the production of all tested virulence factors by DTR isolates, and the percentages of inhibition ranged from 21.5 to 100%. Additionally, β-carotene-treated biofilms showed a significant reduction in biomass and thickness (up to 60%). Moreover, the production of virulence-associated genes, namely <i>lasR</i>, <i>rhlR</i>, and <i>pqsR</i> genes, was downregulated by 0.5 MIC of β-carotene. The molecular docking displayed a resilient LasR-β-carotene complex with a binding free energy of -8.6&#xa0;kcal/mol. The β-carotene-treated rat group showed accelerated wound closure (up to 90% at day 6) and lower <i>Pseudomonas</i> burden (3.3 colony forming unit/g). In addition, the histological examination showed re-epithelialization in the epidermis layer with a few capillaries and newly formed hair follicles in the treated group.</p> Conclusion <p>This is the first study to report the antibacterial, antivirulence, and antiquorum sensing activities of β-carotene against DTR <i>P. aeruginosa</i>, signifying the promising role of β-carotene in mitigating DTR <i>P. aeruginosa</i>-caused infections.</p>

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In vitro and in vivo investigation of the antibacterial, antivirulence, and antiquorum sensing activities of β-carotene against difficult-to-treat resistant Pseudomonas aeruginosa

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月12日

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  • Khaled B. Al-Monofy,
  • Ahmed A. Abdelaziz,
  • Amal M. Abo-Kamar,
  • Lamiaa A. Al-Madboly,
  • Mahmoud H. Farghali

摘要

Background

Difficult-to-treat resistant (DTR) Pseudomonas aeruginosa has strong drug resistance and can tolerate a diversity of antibiotics. Infections triggered by DTR P. aeruginosa urgently require research and development of innovative antibiotics. β-Carotene is a carotenoid pigment with multiple activities, such as antibacterial, antifungal, antioxidant, and anticancer activities, therefore, the current study aimed to investigate the potential antipseudomonal activity of β-carotene against DTR P. aeruginosa to find a new treatment option.

Methods

Antimicrobial susceptibility tests were conducted for 100 P. aeruginosa isolates. Well diffusion and broth microdilution techniques were utilized to determine the antibacterial activity of β-carotene. A total of 10 virulence factors (biofilm, pyocyanin, motility, protease, gelatinase, exopolysaccharide, siderophore, hemolysin, pyomelanin, and rhamnolipid) were screened among the tested isolates, and the effect of β-carotene on these virulence factors was assessed. Light microscopy and confocal laser scanning microscopy approaches were established to investigate the effect of β-carotene on biofilm formation by DTR isolates. Molecular analysis, docking study, and the wound infection model further evaluated the antipseudomonal action of β-carotene against DTR isolates.

Results

All tested multidrug-resistant (MDR) and DTR isolates (n = 40) were susceptible to β-carotene (200 µg/ml), with inhibition zones ranging from 10 to 33 mm, recording minimum inhibitory concentration (MIC) values of 12.5 to 100 µg/ml. It was reported that β-carotene reduced the production of all tested virulence factors by DTR isolates, and the percentages of inhibition ranged from 21.5 to 100%. Additionally, β-carotene-treated biofilms showed a significant reduction in biomass and thickness (up to 60%). Moreover, the production of virulence-associated genes, namely lasR, rhlR, and pqsR genes, was downregulated by 0.5 MIC of β-carotene. The molecular docking displayed a resilient LasR-β-carotene complex with a binding free energy of -8.6 kcal/mol. The β-carotene-treated rat group showed accelerated wound closure (up to 90% at day 6) and lower Pseudomonas burden (3.3 colony forming unit/g). In addition, the histological examination showed re-epithelialization in the epidermis layer with a few capillaries and newly formed hair follicles in the treated group.

Conclusion

This is the first study to report the antibacterial, antivirulence, and antiquorum sensing activities of β-carotene against DTR P. aeruginosa, signifying the promising role of β-carotene in mitigating DTR P. aeruginosa-caused infections.