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The quorum-sensing inhibitor furanone C-30 rapidly loses its tobramycin-potentiating activity against Pseudomonas aeruginosa biofilms during experimental evolution

Mona Bové (UGent) , Xuerui Bao (UGent) , Andrea Sass (UGent) , Aurélie Crabbé (UGent) and Tom Coenye (UGent)
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Abstract
The use of quorum-sensing inhibitors (QSI) has been proposed as an alternative strategy to combat antibiotic resistance. QSI reduce the virulence of a pathogen without killing it and it is claimed that resistance to such compounds is less likely to develop, although there is a lack of experimental data supporting this hypothesis. Additionally, such studies are often carried out in conditions that do not mimic the in vivo situation. In the present study, we evaluated whether a combination of the QSI furanone C-30 and the aminoglycoside antibiotic tobramycin would be "evolution-proof" when used to eradicate Pseudomonas aeruginosa biofilms grown in a synthetic cystic fibrosis sputum medium. We found that the biofilm-eradicating activity of the tobramycin/furanone C-30 combination already decreased after 5 treatment cycles. The antimicrobial susceptibility of P. aeruginosa to tobramycin decreased 8-fold after 16 cycles of treatment with the tobramycin/furanone C-30 combination. Furthermore, microcalorimetry revealed changes in the metabolic activity of P. aeruginosa exposed to furanone C-30, tobramycin, and the combination. Whole-genome sequencing analysis of the evolved strains exposed to the combination identified mutations in mexT, fusA1, and parS, genes known to be involved in antibiotic resistance. In P. aeruginosa treated with furanone C-30 alone, a deletion in mexT was also observed. Our data indicate that furanone C-30 is not "evolution-proof" and quickly becomes ineffective as a tobramycin potentiator.
Keywords
Pseudomonas aeruginosa, biofilms, cystic fibrosis, quorum sensing, CYSTIC-FIBROSIS, ANTIBIOTIC-RESISTANCE, ELONGATION-FACTOR, MEXT, PAO1, VIRULENCE, MECHANISMS, TRAINS, EFFLUX, GENOME

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MLA
Bové, Mona, et al. “The Quorum-Sensing Inhibitor Furanone C-30 Rapidly Loses Its Tobramycin-Potentiating Activity against Pseudomonas Aeruginosa Biofilms during Experimental Evolution.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 65, no. 7, 2021, doi:10.1128/AAC.00413-21.
APA
Bové, M., Bao, X., Sass, A., Crabbé, A., & Coenye, T. (2021). The quorum-sensing inhibitor furanone C-30 rapidly loses its tobramycin-potentiating activity against Pseudomonas aeruginosa biofilms during experimental evolution. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 65(7). https://doi.org/10.1128/AAC.00413-21
Chicago author-date
Bové, Mona, Xuerui Bao, Andrea Sass, Aurélie Crabbé, and Tom Coenye. 2021. “The Quorum-Sensing Inhibitor Furanone C-30 Rapidly Loses Its Tobramycin-Potentiating Activity against Pseudomonas Aeruginosa Biofilms during Experimental Evolution.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 65 (7). https://doi.org/10.1128/AAC.00413-21.
Chicago author-date (all authors)
Bové, Mona, Xuerui Bao, Andrea Sass, Aurélie Crabbé, and Tom Coenye. 2021. “The Quorum-Sensing Inhibitor Furanone C-30 Rapidly Loses Its Tobramycin-Potentiating Activity against Pseudomonas Aeruginosa Biofilms during Experimental Evolution.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 65 (7). doi:10.1128/AAC.00413-21.
Vancouver
1.
Bové M, Bao X, Sass A, Crabbé A, Coenye T. The quorum-sensing inhibitor furanone C-30 rapidly loses its tobramycin-potentiating activity against Pseudomonas aeruginosa biofilms during experimental evolution. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2021;65(7).
IEEE
[1]
M. Bové, X. Bao, A. Sass, A. Crabbé, and T. Coenye, “The quorum-sensing inhibitor furanone C-30 rapidly loses its tobramycin-potentiating activity against Pseudomonas aeruginosa biofilms during experimental evolution,” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 65, no. 7, 2021.
@article{8717722,
  abstract     = {{The use of quorum-sensing inhibitors (QSI) has been proposed as an alternative strategy to combat antibiotic resistance. QSI reduce the virulence of a pathogen without killing it and it is claimed that resistance to such compounds is less likely to develop, although there is a lack of experimental data supporting this hypothesis. Additionally, such studies are often carried out in conditions that do not mimic the in vivo situation. In the present study, we evaluated whether a combination of the QSI furanone C-30 and the aminoglycoside antibiotic tobramycin would be "evolution-proof" when used to eradicate Pseudomonas aeruginosa biofilms grown in a synthetic cystic fibrosis sputum medium. We found that the biofilm-eradicating activity of the tobramycin/furanone C-30 combination already decreased after 5 treatment cycles. The antimicrobial susceptibility of P. aeruginosa to tobramycin decreased 8-fold after 16 cycles of treatment with the tobramycin/furanone C-30 combination. Furthermore, microcalorimetry revealed changes in the metabolic activity of P. aeruginosa exposed to furanone C-30, tobramycin, and the combination. Whole-genome sequencing analysis of the evolved strains exposed to the combination identified mutations in mexT, fusA1, and parS, genes known to be involved in antibiotic resistance. In P. aeruginosa treated with furanone C-30 alone, a deletion in mexT was also observed. Our data indicate that furanone C-30 is not "evolution-proof" and quickly becomes ineffective as a tobramycin potentiator.}},
  articleno    = {{e00413-21}},
  author       = {{Bové, Mona and Bao, Xuerui and Sass, Andrea and Crabbé, Aurélie and Coenye, Tom}},
  issn         = {{0066-4804}},
  journal      = {{ANTIMICROBIAL AGENTS AND CHEMOTHERAPY}},
  keywords     = {{Pseudomonas aeruginosa,biofilms,cystic fibrosis,quorum sensing,CYSTIC-FIBROSIS,ANTIBIOTIC-RESISTANCE,ELONGATION-FACTOR,MEXT,PAO1,VIRULENCE,MECHANISMS,TRAINS,EFFLUX,GENOME}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{11}},
  title        = {{The quorum-sensing inhibitor furanone C-30 rapidly loses its tobramycin-potentiating activity against Pseudomonas aeruginosa biofilms during experimental evolution}},
  url          = {{http://doi.org/10.1128/AAC.00413-21}},
  volume       = {{65}},
  year         = {{2021}},
}

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