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Exposure of Pseudomonas aeruginosa to Cinnamaldehyde Selects Multidrug Resistant Mutants

Cinnamaldehyde (CNA), the main component of cinnamon essential oil, is one of the most active plant compounds against nosocomial pathogen Pseudomonas aeruginosa. Exposure of wild-type strain PA14 (MIC 700 µg/mL) for 5 to 10 days to fixed (900 µg/mL) or increasing (from 900 to 1400 µg/mL) concentrati...

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Autores principales: Tetard, Alexandre, Gaillot, Susie, Dubois, Eline, Aarras, Soumaya, Valot, Benoît, Phan, Gilles, Plésiat, Patrick, Llanes, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774640/
https://www.ncbi.nlm.nih.gov/pubmed/36551447
http://dx.doi.org/10.3390/antibiotics11121790
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author Tetard, Alexandre
Gaillot, Susie
Dubois, Eline
Aarras, Soumaya
Valot, Benoît
Phan, Gilles
Plésiat, Patrick
Llanes, Catherine
author_facet Tetard, Alexandre
Gaillot, Susie
Dubois, Eline
Aarras, Soumaya
Valot, Benoît
Phan, Gilles
Plésiat, Patrick
Llanes, Catherine
author_sort Tetard, Alexandre
collection PubMed
description Cinnamaldehyde (CNA), the main component of cinnamon essential oil, is one of the most active plant compounds against nosocomial pathogen Pseudomonas aeruginosa. Exposure of wild-type strain PA14 (MIC 700 µg/mL) for 5 to 10 days to fixed (900 µg/mL) or increasing (from 900 to 1400 µg/mL) concentrations of this natural antibacterial resulted in emergence of resistant mutants CNA-A1 to A3, and CNA-B1 to B7, respectively. Genome sequencing experiments showed that each of CNA-A1 to A3 mutants differed from PA14 by one SNP, and a slight increase in CNA resistance level (from 700 to 900 µg/mL). By comparison, mutants B1 to B7 were more resistant (up to 1100 µg/mL); each of them harbored multiple SNPs (from 24 to 39) likely as a consequence of alteration of DNA mismatch repair gene mutS. Of the ten mutants selected, eight contained mutations in gene nalC, which indirectly downregulates expression of the operon that codes for multidrug efflux system MexAB-OprM, and showed increased resistance (up to 16-fold versus PA14) to antibiotic molecules exported by the pump, including ß-lactams and fluoroquinolones. Of the six mutants with the highest CNA resistance, five were no longer motile because of alteration of genes flgJ, fliE and/or pilJ genes. Altogether, our data show that P. aeruginosa is able to adapt to strong electrophilic molecules such as CNA by upregulating its intrinsic efflux pump MexAB-OprM, and through less well-characterized pleiotropic changes. Whether multidrug-resistant mutants can emerge in patients using cinnamon essential oil as self-medication needs to be assessed further.
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spelling pubmed-97746402022-12-23 Exposure of Pseudomonas aeruginosa to Cinnamaldehyde Selects Multidrug Resistant Mutants Tetard, Alexandre Gaillot, Susie Dubois, Eline Aarras, Soumaya Valot, Benoît Phan, Gilles Plésiat, Patrick Llanes, Catherine Antibiotics (Basel) Article Cinnamaldehyde (CNA), the main component of cinnamon essential oil, is one of the most active plant compounds against nosocomial pathogen Pseudomonas aeruginosa. Exposure of wild-type strain PA14 (MIC 700 µg/mL) for 5 to 10 days to fixed (900 µg/mL) or increasing (from 900 to 1400 µg/mL) concentrations of this natural antibacterial resulted in emergence of resistant mutants CNA-A1 to A3, and CNA-B1 to B7, respectively. Genome sequencing experiments showed that each of CNA-A1 to A3 mutants differed from PA14 by one SNP, and a slight increase in CNA resistance level (from 700 to 900 µg/mL). By comparison, mutants B1 to B7 were more resistant (up to 1100 µg/mL); each of them harbored multiple SNPs (from 24 to 39) likely as a consequence of alteration of DNA mismatch repair gene mutS. Of the ten mutants selected, eight contained mutations in gene nalC, which indirectly downregulates expression of the operon that codes for multidrug efflux system MexAB-OprM, and showed increased resistance (up to 16-fold versus PA14) to antibiotic molecules exported by the pump, including ß-lactams and fluoroquinolones. Of the six mutants with the highest CNA resistance, five were no longer motile because of alteration of genes flgJ, fliE and/or pilJ genes. Altogether, our data show that P. aeruginosa is able to adapt to strong electrophilic molecules such as CNA by upregulating its intrinsic efflux pump MexAB-OprM, and through less well-characterized pleiotropic changes. Whether multidrug-resistant mutants can emerge in patients using cinnamon essential oil as self-medication needs to be assessed further. MDPI 2022-12-10 /pmc/articles/PMC9774640/ /pubmed/36551447 http://dx.doi.org/10.3390/antibiotics11121790 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tetard, Alexandre
Gaillot, Susie
Dubois, Eline
Aarras, Soumaya
Valot, Benoît
Phan, Gilles
Plésiat, Patrick
Llanes, Catherine
Exposure of Pseudomonas aeruginosa to Cinnamaldehyde Selects Multidrug Resistant Mutants
title Exposure of Pseudomonas aeruginosa to Cinnamaldehyde Selects Multidrug Resistant Mutants
title_full Exposure of Pseudomonas aeruginosa to Cinnamaldehyde Selects Multidrug Resistant Mutants
title_fullStr Exposure of Pseudomonas aeruginosa to Cinnamaldehyde Selects Multidrug Resistant Mutants
title_full_unstemmed Exposure of Pseudomonas aeruginosa to Cinnamaldehyde Selects Multidrug Resistant Mutants
title_short Exposure of Pseudomonas aeruginosa to Cinnamaldehyde Selects Multidrug Resistant Mutants
title_sort exposure of pseudomonas aeruginosa to cinnamaldehyde selects multidrug resistant mutants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9774640/
https://www.ncbi.nlm.nih.gov/pubmed/36551447
http://dx.doi.org/10.3390/antibiotics11121790
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