Exopolysaccharide-Repressing Small Molecules with Antibiofilm and Antivirulence Activity against Pseudomonas aeruginosa
Biofilm formation is a universal virulence strategy in which bacteria grow in dense microbial communities enmeshed within a polymeric extracellular matrix that protects them from antibiotic exposure and the immune system. is an archetypal biofilm-forming organism that utilizes a biofilm growth strat...
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creator | van Tilburg Bernardes, Erik Charron-Mazenod, Laetitia Reading, David J Reckseidler-Zenteno, Shauna L Lewenza, Shawn |
description | Biofilm formation is a universal virulence strategy in which bacteria grow in dense microbial communities enmeshed within a polymeric extracellular matrix that protects them from antibiotic exposure and the immune system.
is an archetypal biofilm-forming organism that utilizes a biofilm growth strategy to cause chronic lung infections in cystic fibrosis (CF) patients. The extracellular matrix of
biofilms is comprised mainly of exopolysaccharides (EPS) and DNA. Both mucoid and nonmucoid isolates of
produce the Pel and Psl EPS, each of which have important roles in antibiotic resistance, biofilm formation, and immune evasion. Given the central importance of the EPS for biofilms, they are attractive targets for novel anti-infective compounds. In this study, we used a high-throughput gene expression screen to identify compounds that repress expression of the
genes. The
repressors demonstrated antibiofilm activity against microplate and flow chamber biofilms formed by wild-type and hyperbiofilm-forming strains. To determine the potential role of EPS in virulence,
/
mutants were shown to have reduced virulence in feeding behavior and slow killing virulence assays in
The antibiofilm molecules also reduced
PAO1 virulence in the nematode slow killing model. Importantly, the combination of antibiotics and antibiofilm compounds increased killing of
biofilms. These small molecules represent a novel anti-infective strategy for the possible treatment of chronic
infections. |
doi_str_mv | 10.1128/AAC.01997-16 |
format | Article |
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is an archetypal biofilm-forming organism that utilizes a biofilm growth strategy to cause chronic lung infections in cystic fibrosis (CF) patients. The extracellular matrix of
biofilms is comprised mainly of exopolysaccharides (EPS) and DNA. Both mucoid and nonmucoid isolates of
produce the Pel and Psl EPS, each of which have important roles in antibiotic resistance, biofilm formation, and immune evasion. Given the central importance of the EPS for biofilms, they are attractive targets for novel anti-infective compounds. In this study, we used a high-throughput gene expression screen to identify compounds that repress expression of the
genes. The
repressors demonstrated antibiofilm activity against microplate and flow chamber biofilms formed by wild-type and hyperbiofilm-forming strains. To determine the potential role of EPS in virulence,
/
mutants were shown to have reduced virulence in feeding behavior and slow killing virulence assays in
The antibiofilm molecules also reduced
PAO1 virulence in the nematode slow killing model. Importantly, the combination of antibiotics and antibiofilm compounds increased killing of
biofilms. These small molecules represent a novel anti-infective strategy for the possible treatment of chronic
infections.</description><identifier>ISSN: 0066-4804</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AAC.01997-16</identifier><identifier>PMID: 28223377</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Animals ; Anti-Bacterial Agents ; Anti-Bacterial Agents - metabolism ; Anti-Bacterial Agents - pharmacology ; Biofilms ; Biofilms - growth & development ; Caenorhabditis elegans ; Caenorhabditis elegans - microbiology ; Clinical Therapeutics ; DNA, Bacterial - metabolism ; Extracellular Matrix - drug effects ; Extracellular Matrix - microbiology ; High-Throughput Screening Assays ; Humans ; Nematoda ; Polysaccharides, Bacterial ; Polysaccharides, Bacterial - antagonists & inhibitors ; Polysaccharides, Bacterial - metabolism ; Pseudomonas aeruginosa ; Pseudomonas aeruginosa - drug effects ; Pseudomonas aeruginosa - isolation & purification ; Pseudomonas aeruginosa - pathogenicity ; Pseudomonas Infections - drug therapy ; Pseudomonas Infections - microbiology ; Repressor Proteins ; Repressor Proteins - metabolism ; Repressor Proteins - pharmacology ; Virulence - genetics</subject><ispartof>Antimicrobial agents and chemotherapy, 2017-05, Vol.61 (5)</ispartof><rights>Copyright © 2017 American Society for Microbiology.</rights><rights>Copyright © 2017 American Society for Microbiology. 2017 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a451t-24064f5afc2133683bdd623798b4def4aac394b781bfc27569a787f3caaab2803</citedby><cites>FETCH-LOGICAL-a451t-24064f5afc2133683bdd623798b4def4aac394b781bfc27569a787f3caaab2803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404518/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404518/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28223377$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van Tilburg Bernardes, Erik</creatorcontrib><creatorcontrib>Charron-Mazenod, Laetitia</creatorcontrib><creatorcontrib>Reading, David J</creatorcontrib><creatorcontrib>Reckseidler-Zenteno, Shauna L</creatorcontrib><creatorcontrib>Lewenza, Shawn</creatorcontrib><title>Exopolysaccharide-Repressing Small Molecules with Antibiofilm and Antivirulence Activity against Pseudomonas aeruginosa</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><description>Biofilm formation is a universal virulence strategy in which bacteria grow in dense microbial communities enmeshed within a polymeric extracellular matrix that protects them from antibiotic exposure and the immune system.
is an archetypal biofilm-forming organism that utilizes a biofilm growth strategy to cause chronic lung infections in cystic fibrosis (CF) patients. The extracellular matrix of
biofilms is comprised mainly of exopolysaccharides (EPS) and DNA. Both mucoid and nonmucoid isolates of
produce the Pel and Psl EPS, each of which have important roles in antibiotic resistance, biofilm formation, and immune evasion. Given the central importance of the EPS for biofilms, they are attractive targets for novel anti-infective compounds. In this study, we used a high-throughput gene expression screen to identify compounds that repress expression of the
genes. The
repressors demonstrated antibiofilm activity against microplate and flow chamber biofilms formed by wild-type and hyperbiofilm-forming strains. To determine the potential role of EPS in virulence,
/
mutants were shown to have reduced virulence in feeding behavior and slow killing virulence assays in
The antibiofilm molecules also reduced
PAO1 virulence in the nematode slow killing model. Importantly, the combination of antibiotics and antibiofilm compounds increased killing of
biofilms. These small molecules represent a novel anti-infective strategy for the possible treatment of chronic
infections.</description><subject>Animals</subject><subject>Anti-Bacterial Agents</subject><subject>Anti-Bacterial Agents - metabolism</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Biofilms</subject><subject>Biofilms - growth & development</subject><subject>Caenorhabditis elegans</subject><subject>Caenorhabditis elegans - microbiology</subject><subject>Clinical Therapeutics</subject><subject>DNA, Bacterial - metabolism</subject><subject>Extracellular Matrix - drug effects</subject><subject>Extracellular Matrix - microbiology</subject><subject>High-Throughput Screening Assays</subject><subject>Humans</subject><subject>Nematoda</subject><subject>Polysaccharides, Bacterial</subject><subject>Polysaccharides, Bacterial - antagonists & inhibitors</subject><subject>Polysaccharides, Bacterial - metabolism</subject><subject>Pseudomonas aeruginosa</subject><subject>Pseudomonas aeruginosa - drug effects</subject><subject>Pseudomonas aeruginosa - isolation & purification</subject><subject>Pseudomonas aeruginosa - pathogenicity</subject><subject>Pseudomonas Infections - drug therapy</subject><subject>Pseudomonas Infections - microbiology</subject><subject>Repressor Proteins</subject><subject>Repressor Proteins - metabolism</subject><subject>Repressor Proteins - pharmacology</subject><subject>Virulence - genetics</subject><issn>0066-4804</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1rFDEchoModq3ePMscLTg1X5NkLsKw1A-oKH6cw28ymd2UTLImM63735vt1qIHwVN4ycPLmzwIPSf4nBCqXnfd-hyTtpU1EQ_QiuBW1aJpxUO0wliImivMT9CTnK9wyU2LH6MTqihlTMoVurn4GXfR7zMYs4XkBlt_sbtkc3ZhU32dwPvqY_TWLN7m6sbN26oLs-tdHJ2fKgjDbb52qQDB2KozhzTvK9iAC3muPme7DHGKAXIFNi0bF2KGp-jRCD7bZ3fnKfr-9uLb-n19-endh3V3WQNvyFxTjgUfGxgNJYwJxfphEJTJVvV8sCMHMKzlvVSkL4hsRAtSyZEZAOipwuwUvTn27pZ-soOxYU7g9S65CdJeR3D675vgtnoTr3XDcVmgSsHLu4IUfyw2z3py2VjvIdi4ZE1UK8swwuR_oLLIEbg5zHp1RE2KOSc73i8iWB-06qJV32rVRBT87IhDnqi-iksK5dP-xb7488X3xb-ds18FR622</recordid><startdate>20170501</startdate><enddate>20170501</enddate><creator>van Tilburg Bernardes, Erik</creator><creator>Charron-Mazenod, Laetitia</creator><creator>Reading, David J</creator><creator>Reckseidler-Zenteno, Shauna L</creator><creator>Lewenza, Shawn</creator><general>American Society for Microbiology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QL</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20170501</creationdate><title>Exopolysaccharide-Repressing Small Molecules with Antibiofilm and Antivirulence Activity against Pseudomonas aeruginosa</title><author>van Tilburg Bernardes, Erik ; Charron-Mazenod, Laetitia ; Reading, David J ; Reckseidler-Zenteno, Shauna L ; Lewenza, Shawn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a451t-24064f5afc2133683bdd623798b4def4aac394b781bfc27569a787f3caaab2803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents</topic><topic>Anti-Bacterial Agents - metabolism</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Biofilms</topic><topic>Biofilms - growth & development</topic><topic>Caenorhabditis elegans</topic><topic>Caenorhabditis elegans - microbiology</topic><topic>Clinical Therapeutics</topic><topic>DNA, Bacterial - metabolism</topic><topic>Extracellular Matrix - drug effects</topic><topic>Extracellular Matrix - microbiology</topic><topic>High-Throughput Screening Assays</topic><topic>Humans</topic><topic>Nematoda</topic><topic>Polysaccharides, Bacterial</topic><topic>Polysaccharides, Bacterial - antagonists & inhibitors</topic><topic>Polysaccharides, Bacterial - metabolism</topic><topic>Pseudomonas aeruginosa</topic><topic>Pseudomonas aeruginosa - drug effects</topic><topic>Pseudomonas aeruginosa - isolation & purification</topic><topic>Pseudomonas aeruginosa - pathogenicity</topic><topic>Pseudomonas Infections - drug therapy</topic><topic>Pseudomonas Infections - microbiology</topic><topic>Repressor Proteins</topic><topic>Repressor Proteins - metabolism</topic><topic>Repressor Proteins - pharmacology</topic><topic>Virulence - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van Tilburg Bernardes, Erik</creatorcontrib><creatorcontrib>Charron-Mazenod, Laetitia</creatorcontrib><creatorcontrib>Reading, David J</creatorcontrib><creatorcontrib>Reckseidler-Zenteno, Shauna L</creatorcontrib><creatorcontrib>Lewenza, Shawn</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antimicrobial agents and chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van Tilburg Bernardes, Erik</au><au>Charron-Mazenod, Laetitia</au><au>Reading, David J</au><au>Reckseidler-Zenteno, Shauna L</au><au>Lewenza, Shawn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exopolysaccharide-Repressing Small Molecules with Antibiofilm and Antivirulence Activity against Pseudomonas aeruginosa</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2017-05-01</date><risdate>2017</risdate><volume>61</volume><issue>5</issue><issn>0066-4804</issn><eissn>1098-6596</eissn><abstract>Biofilm formation is a universal virulence strategy in which bacteria grow in dense microbial communities enmeshed within a polymeric extracellular matrix that protects them from antibiotic exposure and the immune system.
is an archetypal biofilm-forming organism that utilizes a biofilm growth strategy to cause chronic lung infections in cystic fibrosis (CF) patients. The extracellular matrix of
biofilms is comprised mainly of exopolysaccharides (EPS) and DNA. Both mucoid and nonmucoid isolates of
produce the Pel and Psl EPS, each of which have important roles in antibiotic resistance, biofilm formation, and immune evasion. Given the central importance of the EPS for biofilms, they are attractive targets for novel anti-infective compounds. In this study, we used a high-throughput gene expression screen to identify compounds that repress expression of the
genes. The
repressors demonstrated antibiofilm activity against microplate and flow chamber biofilms formed by wild-type and hyperbiofilm-forming strains. To determine the potential role of EPS in virulence,
/
mutants were shown to have reduced virulence in feeding behavior and slow killing virulence assays in
The antibiofilm molecules also reduced
PAO1 virulence in the nematode slow killing model. Importantly, the combination of antibiotics and antibiofilm compounds increased killing of
biofilms. These small molecules represent a novel anti-infective strategy for the possible treatment of chronic
infections.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>28223377</pmid><doi>10.1128/AAC.01997-16</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
subjects | Animals Anti-Bacterial Agents Anti-Bacterial Agents - metabolism Anti-Bacterial Agents - pharmacology Biofilms Biofilms - growth & development Caenorhabditis elegans Caenorhabditis elegans - microbiology Clinical Therapeutics DNA, Bacterial - metabolism Extracellular Matrix - drug effects Extracellular Matrix - microbiology High-Throughput Screening Assays Humans Nematoda Polysaccharides, Bacterial Polysaccharides, Bacterial - antagonists & inhibitors Polysaccharides, Bacterial - metabolism Pseudomonas aeruginosa Pseudomonas aeruginosa - drug effects Pseudomonas aeruginosa - isolation & purification Pseudomonas aeruginosa - pathogenicity Pseudomonas Infections - drug therapy Pseudomonas Infections - microbiology Repressor Proteins Repressor Proteins - metabolism Repressor Proteins - pharmacology Virulence - genetics |
title | Exopolysaccharide-Repressing Small Molecules with Antibiofilm and Antivirulence Activity against Pseudomonas aeruginosa |
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