Role of the two-component system AmgRS in early resistance of Pseudomonas aeruginosa to cinnamaldehyde

ABSTRACT Exposure of Pseudomonas aeruginosa to cinnamaldehyde (CNA), a natural electrophilic antimicrobial often used as self-medication to treat mild infections, triggers overproduction of the MexAB-OprM efflux system, leading to multidrug resistance. In this study, we demonstrate that CNA exposure...

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Main Authors: Eline Dubois, Vladimir Spasovski, Patrick Plésiat, Catherine Llanes
Format: Article
Language:English
Published: American Society for Microbiology 2025-01-01
Series:Microbiology Spectrum
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Online Access:https://journals.asm.org/doi/10.1128/spectrum.01699-24
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author Eline Dubois
Vladimir Spasovski
Patrick Plésiat
Catherine Llanes
author_facet Eline Dubois
Vladimir Spasovski
Patrick Plésiat
Catherine Llanes
author_sort Eline Dubois
collection DOAJ
description ABSTRACT Exposure of Pseudomonas aeruginosa to cinnamaldehyde (CNA), a natural electrophilic antimicrobial often used as self-medication to treat mild infections, triggers overproduction of the MexAB-OprM efflux system, leading to multidrug resistance. In this study, we demonstrate that CNA exposure induces expression of genes regulated by the two-component system AmgRS. AmgRS activates MexAB-OprM production, independent of repressors MexR and NalD. In addition to the essential role played by the NalC-ArmR pathway in this adaptive process, AmgRS is critical for the survival of P. aeruginosa challenged with CNA. Altogether, these data suggest that efflux-dependent and -independent mechanisms are activated in the early phase of CNA exposure, allowing for progressive enzymatic reduction of the biocide to non-toxic cinnamic alcohol.IMPORTANCEExposure of Pseudomonas aeruginosa to cinnamaldehyde (CNA), an antimicrobial used in self-medication, induces overproduction of the MexAB-OprM efflux system, leading to multidrug resistance. Our study demonstrates that the AmgRS two-component system aids in the survival of P. aeruginosa strain PA14 under CNA exposure through both MexAB-OprM-dependent and -independent mechanisms until the enzymatic reduction of CNA into the less toxic cinnamic alcohol. This discovery highlights the pivotal role of AmgRS in mediating defense against aldehyde biocides, emphasizing its significance in the persistence of P. aeruginosa, a pathogen associated with hospital-acquired infections and cystic fibrosis, and underscores the potential impact on clinical treatment strategies.
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spelling doaj-art-0d7b2b683fee4c7891c69ee72ebbd5232025-01-07T14:05:18ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-01-0113110.1128/spectrum.01699-24Role of the two-component system AmgRS in early resistance of Pseudomonas aeruginosa to cinnamaldehydeEline Dubois0Vladimir Spasovski1Patrick Plésiat2Catherine Llanes3UMR CNRS 6249 Chrono-Environnement, UFR Santé, Université Bourgogne Franche-Comté, Besançon, FranceUMR CNRS 6249 Chrono-Environnement, UFR Santé, Université Bourgogne Franche-Comté, Besançon, FranceUMR CNRS 6249 Chrono-Environnement, UFR Santé, Université Bourgogne Franche-Comté, Besançon, FranceUMR CNRS 6249 Chrono-Environnement, UFR Santé, Université Bourgogne Franche-Comté, Besançon, FranceABSTRACT Exposure of Pseudomonas aeruginosa to cinnamaldehyde (CNA), a natural electrophilic antimicrobial often used as self-medication to treat mild infections, triggers overproduction of the MexAB-OprM efflux system, leading to multidrug resistance. In this study, we demonstrate that CNA exposure induces expression of genes regulated by the two-component system AmgRS. AmgRS activates MexAB-OprM production, independent of repressors MexR and NalD. In addition to the essential role played by the NalC-ArmR pathway in this adaptive process, AmgRS is critical for the survival of P. aeruginosa challenged with CNA. Altogether, these data suggest that efflux-dependent and -independent mechanisms are activated in the early phase of CNA exposure, allowing for progressive enzymatic reduction of the biocide to non-toxic cinnamic alcohol.IMPORTANCEExposure of Pseudomonas aeruginosa to cinnamaldehyde (CNA), an antimicrobial used in self-medication, induces overproduction of the MexAB-OprM efflux system, leading to multidrug resistance. Our study demonstrates that the AmgRS two-component system aids in the survival of P. aeruginosa strain PA14 under CNA exposure through both MexAB-OprM-dependent and -independent mechanisms until the enzymatic reduction of CNA into the less toxic cinnamic alcohol. This discovery highlights the pivotal role of AmgRS in mediating defense against aldehyde biocides, emphasizing its significance in the persistence of P. aeruginosa, a pathogen associated with hospital-acquired infections and cystic fibrosis, and underscores the potential impact on clinical treatment strategies.https://journals.asm.org/doi/10.1128/spectrum.01699-24Pseudomonas aeruginosacinnamaldehydetwo-component regulatory systemsefflux pumpsantibiotic resistancecross resistance antibiotics essential oils
spellingShingle Eline Dubois
Vladimir Spasovski
Patrick Plésiat
Catherine Llanes
Role of the two-component system AmgRS in early resistance of Pseudomonas aeruginosa to cinnamaldehyde
Microbiology Spectrum
Pseudomonas aeruginosa
cinnamaldehyde
two-component regulatory systems
efflux pumps
antibiotic resistance
cross resistance antibiotics essential oils
title Role of the two-component system AmgRS in early resistance of Pseudomonas aeruginosa to cinnamaldehyde
title_full Role of the two-component system AmgRS in early resistance of Pseudomonas aeruginosa to cinnamaldehyde
title_fullStr Role of the two-component system AmgRS in early resistance of Pseudomonas aeruginosa to cinnamaldehyde
title_full_unstemmed Role of the two-component system AmgRS in early resistance of Pseudomonas aeruginosa to cinnamaldehyde
title_short Role of the two-component system AmgRS in early resistance of Pseudomonas aeruginosa to cinnamaldehyde
title_sort role of the two component system amgrs in early resistance of pseudomonas aeruginosa to cinnamaldehyde
topic Pseudomonas aeruginosa
cinnamaldehyde
two-component regulatory systems
efflux pumps
antibiotic resistance
cross resistance antibiotics essential oils
url https://journals.asm.org/doi/10.1128/spectrum.01699-24
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AT patrickplesiat roleofthetwocomponentsystemamgrsinearlyresistanceofpseudomonasaeruginosatocinnamaldehyde
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