Natural quorum sensing inhibitors effectively downregulate gene expression of Pseudomonas aeruginosa virulence factors
At present, anti-virulence drugs are being considered as potential therapeutic alternatives and/or adjuvants to currently failing antibiotics. These drugs do not kill bacteria but inhibit virulence factors essential for establishing infection and pathogenesis through targeting non-essential metaboli...
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creator | Ahmed, Syed A. K. S. Rudden, Michelle Smyth, Thomas J. Dooley, James S. G. Marchant, Roger Banat, Ibrahim M. |
description | At present, anti-virulence drugs are being considered as potential therapeutic alternatives and/or adjuvants to currently failing antibiotics. These drugs do not kill bacteria but inhibit virulence factors essential for establishing infection and pathogenesis through targeting non-essential metabolic pathways reducing the selective pressure to develop resistance. We investigated the effect of naturally isolated plant compounds on the repression of the quorum sensing (QS) system which is linked to virulence/pathogenicity in
Pseudomonas aeruginosa
. Our results show that
trans
-cinnamaldehyde (CA) and salicylic acid (SA) significantly inhibit expression of QS regulatory and virulence genes in
P. aeruginosa
PAO1 at sub-inhibitory levels without any bactericidal effect. CA effectively downregulated both the
las
and
rhl
QS systems with
lasI
and
lasR
levels inhibited by 13- and 7-fold respectively compared to 3- and 2-fold reductions with SA treatment, during the stationary growth phase. The QS inhibitors (QSI) also reduced the production of extracellular virulence factors with CA reducing protease, elastase and pyocyanin by 65%, 22% and 32%, respectively. The QSIs significantly reduced biofilm formation and concomitantly with repressed rhamnolipid gene expression, only trace amount of extracellular rhamnolipids were detected. The QSIs did not completely inhibit virulence factor expression and production but their administration significantly lowered the virulence phenotypes at both the transcriptional and extracellular levels. This study shows the significant inhibitory effect of natural plant-derived compounds on the repression of QS systems in
P. aeruginosa
. |
doi_str_mv | 10.1007/s00253-019-09618-0 |
format | Article |
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Pseudomonas aeruginosa
. Our results show that
trans
-cinnamaldehyde (CA) and salicylic acid (SA) significantly inhibit expression of QS regulatory and virulence genes in
P. aeruginosa
PAO1 at sub-inhibitory levels without any bactericidal effect. CA effectively downregulated both the
las
and
rhl
QS systems with
lasI
and
lasR
levels inhibited by 13- and 7-fold respectively compared to 3- and 2-fold reductions with SA treatment, during the stationary growth phase. The QS inhibitors (QSI) also reduced the production of extracellular virulence factors with CA reducing protease, elastase and pyocyanin by 65%, 22% and 32%, respectively. The QSIs significantly reduced biofilm formation and concomitantly with repressed rhamnolipid gene expression, only trace amount of extracellular rhamnolipids were detected. The QSIs did not completely inhibit virulence factor expression and production but their administration significantly lowered the virulence phenotypes at both the transcriptional and extracellular levels. This study shows the significant inhibitory effect of natural plant-derived compounds on the repression of QS systems in
P. aeruginosa
.</description><identifier>ISSN: 0175-7598</identifier><identifier>EISSN: 1432-0614</identifier><identifier>DOI: 10.1007/s00253-019-09618-0</identifier><identifier>PMID: 30852658</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adjuvants ; Analysis ; antibacterial properties ; Antibiotics ; bacteria ; biochemical pathways ; biofilm ; Biofilms ; Biomedical and Life Sciences ; Biotechnology ; Cinnamaldehyde ; Control ; developmental stages ; drugs ; Elastase ; Extracellular levels ; Gene expression ; gene expression regulation ; genes ; Genetic aspects ; Genomics ; Genomics, Transcriptomics, Proteomics ; Inhibitors ; Life Sciences ; Metabolic pathways ; Microbial Genetics and Genomics ; Microbiology ; Pathogenesis ; Pathogenicity ; Pathogens ; phenotype ; Phenotypes ; Plants ; Prevention ; Proteomics ; Pseudomonas aeruginosa ; Pseudomonas aeruginosa infections ; Pyocyanin ; Quorum sensing ; Rhamnolipids ; Salicylic acid ; System effectiveness ; therapeutics ; Transcription ; transcription (genetics) ; Transcriptomics ; Virulence ; Virulence (Microbiology) ; Virulence factors</subject><ispartof>Applied microbiology and biotechnology, 2019-04, Vol.103 (8), p.3521-3535</ispartof><rights>The Author(s) 2019</rights><rights>COPYRIGHT 2019 Springer</rights><rights>Applied Microbiology and Biotechnology is a copyright of Springer, (2019). All Rights Reserved. © 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c711t-478e9cfa8c0042ad5097ac465f1c6fbcc17451517e6e8cedc3b6513ef6f0b3753</citedby><cites>FETCH-LOGICAL-c711t-478e9cfa8c0042ad5097ac465f1c6fbcc17451517e6e8cedc3b6513ef6f0b3753</cites><orcidid>0000-0002-9459-5572</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00253-019-09618-0$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00253-019-09618-0$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30852658$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ahmed, Syed A. K. S.</creatorcontrib><creatorcontrib>Rudden, Michelle</creatorcontrib><creatorcontrib>Smyth, Thomas J.</creatorcontrib><creatorcontrib>Dooley, James S. G.</creatorcontrib><creatorcontrib>Marchant, Roger</creatorcontrib><creatorcontrib>Banat, Ibrahim M.</creatorcontrib><title>Natural quorum sensing inhibitors effectively downregulate gene expression of Pseudomonas aeruginosa virulence factors</title><title>Applied microbiology and biotechnology</title><addtitle>Appl Microbiol Biotechnol</addtitle><addtitle>Appl Microbiol Biotechnol</addtitle><description>At present, anti-virulence drugs are being considered as potential therapeutic alternatives and/or adjuvants to currently failing antibiotics. These drugs do not kill bacteria but inhibit virulence factors essential for establishing infection and pathogenesis through targeting non-essential metabolic pathways reducing the selective pressure to develop resistance. We investigated the effect of naturally isolated plant compounds on the repression of the quorum sensing (QS) system which is linked to virulence/pathogenicity in
Pseudomonas aeruginosa
. Our results show that
trans
-cinnamaldehyde (CA) and salicylic acid (SA) significantly inhibit expression of QS regulatory and virulence genes in
P. aeruginosa
PAO1 at sub-inhibitory levels without any bactericidal effect. CA effectively downregulated both the
las
and
rhl
QS systems with
lasI
and
lasR
levels inhibited by 13- and 7-fold respectively compared to 3- and 2-fold reductions with SA treatment, during the stationary growth phase. The QS inhibitors (QSI) also reduced the production of extracellular virulence factors with CA reducing protease, elastase and pyocyanin by 65%, 22% and 32%, respectively. The QSIs significantly reduced biofilm formation and concomitantly with repressed rhamnolipid gene expression, only trace amount of extracellular rhamnolipids were detected. The QSIs did not completely inhibit virulence factor expression and production but their administration significantly lowered the virulence phenotypes at both the transcriptional and extracellular levels. This study shows the significant inhibitory effect of natural plant-derived compounds on the repression of QS systems in
P. aeruginosa
.</description><subject>Adjuvants</subject><subject>Analysis</subject><subject>antibacterial properties</subject><subject>Antibiotics</subject><subject>bacteria</subject><subject>biochemical pathways</subject><subject>biofilm</subject><subject>Biofilms</subject><subject>Biomedical and Life Sciences</subject><subject>Biotechnology</subject><subject>Cinnamaldehyde</subject><subject>Control</subject><subject>developmental stages</subject><subject>drugs</subject><subject>Elastase</subject><subject>Extracellular levels</subject><subject>Gene expression</subject><subject>gene expression regulation</subject><subject>genes</subject><subject>Genetic aspects</subject><subject>Genomics</subject><subject>Genomics, Transcriptomics, Proteomics</subject><subject>Inhibitors</subject><subject>Life Sciences</subject><subject>Metabolic pathways</subject><subject>Microbial Genetics and Genomics</subject><subject>Microbiology</subject><subject>Pathogenesis</subject><subject>Pathogenicity</subject><subject>Pathogens</subject><subject>phenotype</subject><subject>Phenotypes</subject><subject>Plants</subject><subject>Prevention</subject><subject>Proteomics</subject><subject>Pseudomonas aeruginosa</subject><subject>Pseudomonas aeruginosa infections</subject><subject>Pyocyanin</subject><subject>Quorum sensing</subject><subject>Rhamnolipids</subject><subject>Salicylic acid</subject><subject>System effectiveness</subject><subject>therapeutics</subject><subject>Transcription</subject><subject>transcription (genetics)</subject><subject>Transcriptomics</subject><subject>Virulence</subject><subject>Virulence (Microbiology)</subject><subject>Virulence factors</subject><issn>0175-7598</issn><issn>1432-0614</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kk1v1DAQhiMEokvhD3BAlriUQ8o4sR3nglRVfFSqAPFxtrzeceoqsbd2vLT_Hi9bWhYh5MNInud9RzN6q-o5hWMK0L1OAA1va6B9Db2gsoYH1YKytqlBUPawWgDteN3xXh5UT1K6BKCNFOJxddCC5I3gclFtPuo5Rz2SqxxinkhCn5wfiPMXbunmEBNBa9HMboPjDVmFHz7ikEc9IxnQI8HrdcSUXPAkWPI5YV6FKXidiMaYB-dD0mTjYh7RGyRWm63p0-qR1WPCZ7f1sPr-7u230w_1-af3Z6cn57XpKJ1r1knsjdXSALBGrzj0nTZMcEuNsEtjaMc45bRDgdLgyrRLwWmLVlhYth1vD6s3O991Xk6lj34uy6p1dJOONypop_Y73l2oIWyUYKxvaV8Mjm4NYrjKmGY1uWRwHLXHkJNqmu0YkFQU9OVf6GXI0Zf1VENl3zAGTN5Tgx5ROW9DmWu2puqES9qyVgIt1PE_qPJWODkTPFpX_vcEr_YEhZnxeh50Tkmdff2yzzY71sSQUkR7dw8KapsstUuWKslSv5KloIhe_HnJO8nvKBWg3QGptPyA8X79_9j-BK082wY</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Ahmed, Syed A. K. S.</creator><creator>Rudden, Michelle</creator><creator>Smyth, Thomas J.</creator><creator>Dooley, James S. 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K. S. ; Rudden, Michelle ; Smyth, Thomas J. ; Dooley, James S. G. ; Marchant, Roger ; Banat, Ibrahim M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c711t-478e9cfa8c0042ad5097ac465f1c6fbcc17451517e6e8cedc3b6513ef6f0b3753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adjuvants</topic><topic>Analysis</topic><topic>antibacterial properties</topic><topic>Antibiotics</topic><topic>bacteria</topic><topic>biochemical pathways</topic><topic>biofilm</topic><topic>Biofilms</topic><topic>Biomedical and Life Sciences</topic><topic>Biotechnology</topic><topic>Cinnamaldehyde</topic><topic>Control</topic><topic>developmental stages</topic><topic>drugs</topic><topic>Elastase</topic><topic>Extracellular levels</topic><topic>Gene expression</topic><topic>gene expression regulation</topic><topic>genes</topic><topic>Genetic aspects</topic><topic>Genomics</topic><topic>Genomics, Transcriptomics, Proteomics</topic><topic>Inhibitors</topic><topic>Life Sciences</topic><topic>Metabolic pathways</topic><topic>Microbial Genetics and Genomics</topic><topic>Microbiology</topic><topic>Pathogenesis</topic><topic>Pathogenicity</topic><topic>Pathogens</topic><topic>phenotype</topic><topic>Phenotypes</topic><topic>Plants</topic><topic>Prevention</topic><topic>Proteomics</topic><topic>Pseudomonas aeruginosa</topic><topic>Pseudomonas aeruginosa infections</topic><topic>Pyocyanin</topic><topic>Quorum sensing</topic><topic>Rhamnolipids</topic><topic>Salicylic acid</topic><topic>System effectiveness</topic><topic>therapeutics</topic><topic>Transcription</topic><topic>transcription (genetics)</topic><topic>Transcriptomics</topic><topic>Virulence</topic><topic>Virulence (Microbiology)</topic><topic>Virulence factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ahmed, Syed A. K. S.</creatorcontrib><creatorcontrib>Rudden, Michelle</creatorcontrib><creatorcontrib>Smyth, Thomas J.</creatorcontrib><creatorcontrib>Dooley, James S. 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K. S.</au><au>Rudden, Michelle</au><au>Smyth, Thomas J.</au><au>Dooley, James S. G.</au><au>Marchant, Roger</au><au>Banat, Ibrahim M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Natural quorum sensing inhibitors effectively downregulate gene expression of Pseudomonas aeruginosa virulence factors</atitle><jtitle>Applied microbiology and biotechnology</jtitle><stitle>Appl Microbiol Biotechnol</stitle><addtitle>Appl Microbiol Biotechnol</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>103</volume><issue>8</issue><spage>3521</spage><epage>3535</epage><pages>3521-3535</pages><issn>0175-7598</issn><eissn>1432-0614</eissn><abstract>At present, anti-virulence drugs are being considered as potential therapeutic alternatives and/or adjuvants to currently failing antibiotics. These drugs do not kill bacteria but inhibit virulence factors essential for establishing infection and pathogenesis through targeting non-essential metabolic pathways reducing the selective pressure to develop resistance. We investigated the effect of naturally isolated plant compounds on the repression of the quorum sensing (QS) system which is linked to virulence/pathogenicity in
Pseudomonas aeruginosa
. Our results show that
trans
-cinnamaldehyde (CA) and salicylic acid (SA) significantly inhibit expression of QS regulatory and virulence genes in
P. aeruginosa
PAO1 at sub-inhibitory levels without any bactericidal effect. CA effectively downregulated both the
las
and
rhl
QS systems with
lasI
and
lasR
levels inhibited by 13- and 7-fold respectively compared to 3- and 2-fold reductions with SA treatment, during the stationary growth phase. The QS inhibitors (QSI) also reduced the production of extracellular virulence factors with CA reducing protease, elastase and pyocyanin by 65%, 22% and 32%, respectively. The QSIs significantly reduced biofilm formation and concomitantly with repressed rhamnolipid gene expression, only trace amount of extracellular rhamnolipids were detected. The QSIs did not completely inhibit virulence factor expression and production but their administration significantly lowered the virulence phenotypes at both the transcriptional and extracellular levels. This study shows the significant inhibitory effect of natural plant-derived compounds on the repression of QS systems in
P. aeruginosa
.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>30852658</pmid><doi>10.1007/s00253-019-09618-0</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-9459-5572</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adjuvants Analysis antibacterial properties Antibiotics bacteria biochemical pathways biofilm Biofilms Biomedical and Life Sciences Biotechnology Cinnamaldehyde Control developmental stages drugs Elastase Extracellular levels Gene expression gene expression regulation genes Genetic aspects Genomics Genomics, Transcriptomics, Proteomics Inhibitors Life Sciences Metabolic pathways Microbial Genetics and Genomics Microbiology Pathogenesis Pathogenicity Pathogens phenotype Phenotypes Plants Prevention Proteomics Pseudomonas aeruginosa Pseudomonas aeruginosa infections Pyocyanin Quorum sensing Rhamnolipids Salicylic acid System effectiveness therapeutics Transcription transcription (genetics) Transcriptomics Virulence Virulence (Microbiology) Virulence factors |
title | Natural quorum sensing inhibitors effectively downregulate gene expression of Pseudomonas aeruginosa virulence factors |
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