Tackling <i>Pseudomonas aeruginosa</i> Virulence by Mulinane-Like Diterpenoids from <i>Azorella atacamensis</i>
<i>Pseudomonas aeruginosa</i> is an important multidrug-resistant human pathogen by dint of its high intrinsic, acquired, and adaptive resistance mechanisms, causing great concern for immune-compromised individuals and public health. Additionally, <i>P. aeruginosa</i> resilie...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-12-01
|
Series: | Biomolecules |
Subjects: | |
Online Access: | https://www.mdpi.com/2218-273X/10/12/1626 |
id |
doaj-11ad29e1b72041669155f2fa76559522 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Onyedikachi Cecil Azuama Sergio Ortiz Luis Quirós-Guerrero Emeline Bouffartigues Damien Tortuel Olivier Maillot Marc Feuilloley Pierre Cornelis Olivier Lesouhaitier Raphaël Grougnet Sabrina Boutefnouchet Jean-Luc Wolfender Sylvie Chevalier Ali Tahrioui |
spellingShingle |
Onyedikachi Cecil Azuama Sergio Ortiz Luis Quirós-Guerrero Emeline Bouffartigues Damien Tortuel Olivier Maillot Marc Feuilloley Pierre Cornelis Olivier Lesouhaitier Raphaël Grougnet Sabrina Boutefnouchet Jean-Luc Wolfender Sylvie Chevalier Ali Tahrioui Tackling <i>Pseudomonas aeruginosa</i> Virulence by Mulinane-Like Diterpenoids from <i>Azorella atacamensis</i> Biomolecules mulinane-like diterpenoids <i>Azorella atacamensis</i> anti-virulence <i>Pseudomonas aeruginosa</i> membrane stiffness ECFσ SigX |
author_facet |
Onyedikachi Cecil Azuama Sergio Ortiz Luis Quirós-Guerrero Emeline Bouffartigues Damien Tortuel Olivier Maillot Marc Feuilloley Pierre Cornelis Olivier Lesouhaitier Raphaël Grougnet Sabrina Boutefnouchet Jean-Luc Wolfender Sylvie Chevalier Ali Tahrioui |
author_sort |
Onyedikachi Cecil Azuama |
title |
Tackling <i>Pseudomonas aeruginosa</i> Virulence by Mulinane-Like Diterpenoids from <i>Azorella atacamensis</i> |
title_short |
Tackling <i>Pseudomonas aeruginosa</i> Virulence by Mulinane-Like Diterpenoids from <i>Azorella atacamensis</i> |
title_full |
Tackling <i>Pseudomonas aeruginosa</i> Virulence by Mulinane-Like Diterpenoids from <i>Azorella atacamensis</i> |
title_fullStr |
Tackling <i>Pseudomonas aeruginosa</i> Virulence by Mulinane-Like Diterpenoids from <i>Azorella atacamensis</i> |
title_full_unstemmed |
Tackling <i>Pseudomonas aeruginosa</i> Virulence by Mulinane-Like Diterpenoids from <i>Azorella atacamensis</i> |
title_sort |
tackling <i>pseudomonas aeruginosa</i> virulence by mulinane-like diterpenoids from <i>azorella atacamensis</i> |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2020-12-01 |
description |
<i>Pseudomonas aeruginosa</i> is an important multidrug-resistant human pathogen by dint of its high intrinsic, acquired, and adaptive resistance mechanisms, causing great concern for immune-compromised individuals and public health. Additionally, <i>P. aeruginosa</i> resilience lies in the production of a myriad of virulence factors, which are known to be tightly regulated by the quorum sensing (QS) system. Anti-virulence therapy has been adopted as an innovative alternative approach to circumvent bacterial antibiotic resistance. Since plants are known repositories of natural phytochemicals, herein, we explored the anti-virulence potential of <i>Azorella atacamensis</i>, a medicinal plant from the Taira Atacama community (Calama, Chile), against <i>P. aeruginosa</i>. Interestingly, <i>A. atacamensis</i> extract (<i>Aa</i>E) conferred a significant protection for human lung cells and <i>Caenorhabditis elegans</i> nematodes towards <i>P. aeruginosa</i> pathogenicity. The production of key virulence factors was decreased upon <i>Aa</i>E exposure without affecting <i>P. aeruginosa</i> growth. In addition, <i>Aa</i>E was able to decrease QS-molecules production. Furthermore, metabolite profiling of <i>Aa</i>E and its derived fractions achieved by combination of a molecular network and in silico annotation allowed the putative identification of fourteen diterpenoids bearing a mulinane-like skeleton. Remarkably, this unique interesting group of diterpenoids seems to be responsible for the interference with virulence factors as well as on the perturbation of membrane homeostasis of <i>P. aeruginosa</i>. Hence, there was a significant increase in membrane stiffness, which appears to be modulated by the cell wall stress response ECFσ SigX, an extracytoplasmic function sigma factor involved in membrane homeostasis as well as <i>P. aeruginosa</i> virulence. |
topic |
mulinane-like diterpenoids <i>Azorella atacamensis</i> anti-virulence <i>Pseudomonas aeruginosa</i> membrane stiffness ECFσ SigX |
url |
https://www.mdpi.com/2218-273X/10/12/1626 |
work_keys_str_mv |
AT onyedikachicecilazuama tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT sergioortiz tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT luisquirosguerrero tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT emelinebouffartigues tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT damientortuel tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT oliviermaillot tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT marcfeuilloley tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT pierrecornelis tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT olivierlesouhaitier tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT raphaelgrougnet tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT sabrinaboutefnouchet tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT jeanlucwolfender tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT sylviechevalier tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi AT alitahrioui tacklingipseudomonasaeruginosaivirulencebymulinanelikediterpenoidsfromiazorellaatacamensisi |
_version_ |
1724401701382782976 |
spelling |
doaj-11ad29e1b72041669155f2fa765595222020-12-03T00:02:31ZengMDPI AGBiomolecules2218-273X2020-12-01101626162610.3390/biom10121626Tackling <i>Pseudomonas aeruginosa</i> Virulence by Mulinane-Like Diterpenoids from <i>Azorella atacamensis</i>Onyedikachi Cecil Azuama0Sergio Ortiz1Luis Quirós-Guerrero2Emeline Bouffartigues3Damien Tortuel4Olivier Maillot5Marc Feuilloley6Pierre Cornelis7Olivier Lesouhaitier8Raphaël Grougnet9Sabrina Boutefnouchet10Jean-Luc Wolfender11Sylvie Chevalier12Ali Tahrioui13Laboratoire de Microbiologie Signaux et Microenvironnement, Université de Rouen Normandie, Normandie Université, LMSM EA4312, 27000 Évreux, FranceÉquipe Produits Naturels, Analyses et Synthèses (PNAS), CiTCoM UMR 8038 CNRS, Faculté de Pharmacie, Université de Paris, 75006 Paris, FrancePhytochemistry and Bioactive Natural Products, School of Pharmaceutical Science, University of Geneva, 1211 Geneva, SwitzerlandLaboratoire de Microbiologie Signaux et Microenvironnement, Université de Rouen Normandie, Normandie Université, LMSM EA4312, 27000 Évreux, FranceLaboratoire de Microbiologie Signaux et Microenvironnement, Université de Rouen Normandie, Normandie Université, LMSM EA4312, 27000 Évreux, FranceLaboratoire de Microbiologie Signaux et Microenvironnement, Université de Rouen Normandie, Normandie Université, LMSM EA4312, 27000 Évreux, FranceLaboratoire de Microbiologie Signaux et Microenvironnement, Université de Rouen Normandie, Normandie Université, LMSM EA4312, 27000 Évreux, FranceLaboratoire de Microbiologie Signaux et Microenvironnement, Université de Rouen Normandie, Normandie Université, LMSM EA4312, 27000 Évreux, FranceLaboratoire de Microbiologie Signaux et Microenvironnement, Université de Rouen Normandie, Normandie Université, LMSM EA4312, 27000 Évreux, FranceÉquipe Produits Naturels, Analyses et Synthèses (PNAS), CiTCoM UMR 8038 CNRS, Faculté de Pharmacie, Université de Paris, 75006 Paris, FranceÉquipe Produits Naturels, Analyses et Synthèses (PNAS), CiTCoM UMR 8038 CNRS, Faculté de Pharmacie, Université de Paris, 75006 Paris, FrancePhytochemistry and Bioactive Natural Products, School of Pharmaceutical Science, University of Geneva, 1211 Geneva, SwitzerlandLaboratoire de Microbiologie Signaux et Microenvironnement, Université de Rouen Normandie, Normandie Université, LMSM EA4312, 27000 Évreux, FranceLaboratoire de Microbiologie Signaux et Microenvironnement, Université de Rouen Normandie, Normandie Université, LMSM EA4312, 27000 Évreux, France<i>Pseudomonas aeruginosa</i> is an important multidrug-resistant human pathogen by dint of its high intrinsic, acquired, and adaptive resistance mechanisms, causing great concern for immune-compromised individuals and public health. Additionally, <i>P. aeruginosa</i> resilience lies in the production of a myriad of virulence factors, which are known to be tightly regulated by the quorum sensing (QS) system. Anti-virulence therapy has been adopted as an innovative alternative approach to circumvent bacterial antibiotic resistance. Since plants are known repositories of natural phytochemicals, herein, we explored the anti-virulence potential of <i>Azorella atacamensis</i>, a medicinal plant from the Taira Atacama community (Calama, Chile), against <i>P. aeruginosa</i>. Interestingly, <i>A. atacamensis</i> extract (<i>Aa</i>E) conferred a significant protection for human lung cells and <i>Caenorhabditis elegans</i> nematodes towards <i>P. aeruginosa</i> pathogenicity. The production of key virulence factors was decreased upon <i>Aa</i>E exposure without affecting <i>P. aeruginosa</i> growth. In addition, <i>Aa</i>E was able to decrease QS-molecules production. Furthermore, metabolite profiling of <i>Aa</i>E and its derived fractions achieved by combination of a molecular network and in silico annotation allowed the putative identification of fourteen diterpenoids bearing a mulinane-like skeleton. Remarkably, this unique interesting group of diterpenoids seems to be responsible for the interference with virulence factors as well as on the perturbation of membrane homeostasis of <i>P. aeruginosa</i>. Hence, there was a significant increase in membrane stiffness, which appears to be modulated by the cell wall stress response ECFσ SigX, an extracytoplasmic function sigma factor involved in membrane homeostasis as well as <i>P. aeruginosa</i> virulence.https://www.mdpi.com/2218-273X/10/12/1626mulinane-like diterpenoids<i>Azorella atacamensis</i>anti-virulence<i>Pseudomonas aeruginosa</i>membrane stiffnessECFσ SigX |