2,4-Di-Tert-Butylphenol Isolated From an Endophytic Fungus, Daldinia eschscholtzii, Reduces Virulence and Quorum Sensing in Pseudomonas aeruginosa
Pseudomonas aeruginosa is among the top three gram-negative bacteria according to the WHO’s critical priority list of pathogens against which newer antibiotics are urgently needed and considered a global threat due to multiple drug resistance. This situation demands unconventional antimicrobial stra...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-07-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2020.01668/full |
| _version_ | 1828193663499370496 |
|---|---|
| author | Rashmi Mishra Jai Shanti Kushveer Mohd. Imran K. Khan Sudhakar Pagal Chetan Kumar Meena Ayaluru Murali Arunkumar Dhayalan Vemuri Venkateswara Sarma |
| author_facet | Rashmi Mishra Jai Shanti Kushveer Mohd. Imran K. Khan Sudhakar Pagal Chetan Kumar Meena Ayaluru Murali Arunkumar Dhayalan Vemuri Venkateswara Sarma |
| author_sort | Rashmi Mishra |
| collection | DOAJ |
| description | Pseudomonas aeruginosa is among the top three gram-negative bacteria according to the WHO’s critical priority list of pathogens against which newer antibiotics are urgently needed and considered a global threat due to multiple drug resistance. This situation demands unconventional antimicrobial strategies such as the inhibition of quorum sensing to alleviate the manifestation of classical resistance mechanisms. Here, we report that 2,4-di-tert-butylphenol (2,4-DBP), isolated from an endophytic fungus, Daldinia eschscholtzii, inhibits the quorum-sensing properties of P. aeruginosa. We have found that treating P. aeruginosa with 2,4-DBP substantially reduced the secretion of virulence factors as well as biofilm, and its associated factors that are controlled by quorum sensing, in a dose-dependent manner. Concomitantly, 2,4-DBP also significantly reduced the expression of quorum sensing-related genes, i.e., lasI, lasR, rhlI, and rhlR significantly. Importantly, 2,4-DBP restricted the adhesion and invasion of P. aeruginosa to the A549 lung alveolar carcinoma cells. In addition, bactericidal assay with 2,4-DBP exhibited synergism with ampicillin to kill P. aeruginosa. Furthermore, our computational studies predicted that 2,4-DBP could bind to the P. aeruginosa quorum-sensing receptors LasR and RhlR. Collectively, these data suggest that 2,4-DBP can be exploited as a standalone drug or in combination with antibiotic(s) as an anti-virulence and anti-biofilm agent to combat the multidrug resistant P. aeruginosa infection. |
| first_indexed | 2024-04-12T09:12:14Z |
| format | Article |
| id | doaj.art-014527725195483280f264f1704737d8 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T09:12:14Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-014527725195483280f264f1704737d82022-12-22T03:38:57ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-07-011110.3389/fmicb.2020.016685422012,4-Di-Tert-Butylphenol Isolated From an Endophytic Fungus, Daldinia eschscholtzii, Reduces Virulence and Quorum Sensing in Pseudomonas aeruginosaRashmi Mishra0Jai Shanti Kushveer1Mohd. Imran K. Khan2Sudhakar Pagal3Chetan Kumar Meena4Ayaluru Murali5Arunkumar Dhayalan6Vemuri Venkateswara Sarma7Department of Biotechnology, Pondicherry University, Puducherry, IndiaDepartment of Biotechnology, Pondicherry University, Puducherry, IndiaDepartment of Biotechnology, Pondicherry University, Puducherry, IndiaDepartment of Biotechnology, Pondicherry University, Puducherry, IndiaCentre for Bioinformatics, Pondicherry University, Puducherry, IndiaCentre for Bioinformatics, Pondicherry University, Puducherry, IndiaDepartment of Biotechnology, Pondicherry University, Puducherry, IndiaDepartment of Biotechnology, Pondicherry University, Puducherry, IndiaPseudomonas aeruginosa is among the top three gram-negative bacteria according to the WHO’s critical priority list of pathogens against which newer antibiotics are urgently needed and considered a global threat due to multiple drug resistance. This situation demands unconventional antimicrobial strategies such as the inhibition of quorum sensing to alleviate the manifestation of classical resistance mechanisms. Here, we report that 2,4-di-tert-butylphenol (2,4-DBP), isolated from an endophytic fungus, Daldinia eschscholtzii, inhibits the quorum-sensing properties of P. aeruginosa. We have found that treating P. aeruginosa with 2,4-DBP substantially reduced the secretion of virulence factors as well as biofilm, and its associated factors that are controlled by quorum sensing, in a dose-dependent manner. Concomitantly, 2,4-DBP also significantly reduced the expression of quorum sensing-related genes, i.e., lasI, lasR, rhlI, and rhlR significantly. Importantly, 2,4-DBP restricted the adhesion and invasion of P. aeruginosa to the A549 lung alveolar carcinoma cells. In addition, bactericidal assay with 2,4-DBP exhibited synergism with ampicillin to kill P. aeruginosa. Furthermore, our computational studies predicted that 2,4-DBP could bind to the P. aeruginosa quorum-sensing receptors LasR and RhlR. Collectively, these data suggest that 2,4-DBP can be exploited as a standalone drug or in combination with antibiotic(s) as an anti-virulence and anti-biofilm agent to combat the multidrug resistant P. aeruginosa infection.https://www.frontiersin.org/article/10.3389/fmicb.2020.01668/fullanti-quorum sensing24-Di-tert-butylphenolendophytic fungimultidrug resistanceP. aeruginosa |
| spellingShingle | Rashmi Mishra Jai Shanti Kushveer Mohd. Imran K. Khan Sudhakar Pagal Chetan Kumar Meena Ayaluru Murali Arunkumar Dhayalan Vemuri Venkateswara Sarma 2,4-Di-Tert-Butylphenol Isolated From an Endophytic Fungus, Daldinia eschscholtzii, Reduces Virulence and Quorum Sensing in Pseudomonas aeruginosa Frontiers in Microbiology anti-quorum sensing 2 4-Di-tert-butylphenol endophytic fungi multidrug resistance P. aeruginosa |
| title | 2,4-Di-Tert-Butylphenol Isolated From an Endophytic Fungus, Daldinia eschscholtzii, Reduces Virulence and Quorum Sensing in Pseudomonas aeruginosa |
| title_full | 2,4-Di-Tert-Butylphenol Isolated From an Endophytic Fungus, Daldinia eschscholtzii, Reduces Virulence and Quorum Sensing in Pseudomonas aeruginosa |
| title_fullStr | 2,4-Di-Tert-Butylphenol Isolated From an Endophytic Fungus, Daldinia eschscholtzii, Reduces Virulence and Quorum Sensing in Pseudomonas aeruginosa |
| title_full_unstemmed | 2,4-Di-Tert-Butylphenol Isolated From an Endophytic Fungus, Daldinia eschscholtzii, Reduces Virulence and Quorum Sensing in Pseudomonas aeruginosa |
| title_short | 2,4-Di-Tert-Butylphenol Isolated From an Endophytic Fungus, Daldinia eschscholtzii, Reduces Virulence and Quorum Sensing in Pseudomonas aeruginosa |
| title_sort | 2 4 di tert butylphenol isolated from an endophytic fungus daldinia eschscholtzii reduces virulence and quorum sensing in pseudomonas aeruginosa |
| topic | anti-quorum sensing 2 4-Di-tert-butylphenol endophytic fungi multidrug resistance P. aeruginosa |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2020.01668/full |
| work_keys_str_mv | AT rashmimishra 24ditertbutylphenolisolatedfromanendophyticfungusdaldiniaeschscholtziireducesvirulenceandquorumsensinginpseudomonasaeruginosa AT jaishantikushveer 24ditertbutylphenolisolatedfromanendophyticfungusdaldiniaeschscholtziireducesvirulenceandquorumsensinginpseudomonasaeruginosa AT mohdimrankkhan 24ditertbutylphenolisolatedfromanendophyticfungusdaldiniaeschscholtziireducesvirulenceandquorumsensinginpseudomonasaeruginosa AT sudhakarpagal 24ditertbutylphenolisolatedfromanendophyticfungusdaldiniaeschscholtziireducesvirulenceandquorumsensinginpseudomonasaeruginosa AT chetankumarmeena 24ditertbutylphenolisolatedfromanendophyticfungusdaldiniaeschscholtziireducesvirulenceandquorumsensinginpseudomonasaeruginosa AT ayalurumurali 24ditertbutylphenolisolatedfromanendophyticfungusdaldiniaeschscholtziireducesvirulenceandquorumsensinginpseudomonasaeruginosa AT arunkumardhayalan 24ditertbutylphenolisolatedfromanendophyticfungusdaldiniaeschscholtziireducesvirulenceandquorumsensinginpseudomonasaeruginosa AT vemurivenkateswarasarma 24ditertbutylphenolisolatedfromanendophyticfungusdaldiniaeschscholtziireducesvirulenceandquorumsensinginpseudomonasaeruginosa |