Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.
Quorum sensing (QS) is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress viru...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761573/?tool=EBI |
| _version_ | 1818722635981258752 |
|---|---|
| author | Wai-Leung Ng Lark Perez Jianping Cong Martin F Semmelhack Bonnie L Bassler |
| author_facet | Wai-Leung Ng Lark Perez Jianping Cong Martin F Semmelhack Bonnie L Bassler |
| author_sort | Wai-Leung Ng |
| collection | DOAJ |
| description | Quorum sensing (QS) is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress virulence factor production and biofilm formation. Thus, molecules that activate QS in V. cholerae have the potential to control pathogenicity in this globally important bacterium. Using a whole-cell high-throughput screen, we identified eleven molecules that activate V. cholerae QS: eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. The LuxO inhibitors act by an uncompetitive mechanism by binding to the pre-formed LuxO-ATP complex to inhibit ATP hydrolysis. Genetic analyses suggest that the inhibitors bind in close proximity to the Walker B motif. The inhibitors display broad-spectrum capability in activation of QS in Vibrio species that employ LuxO. To the best of our knowledge, these are the first molecules identified that inhibit the ATPase activity of a NtrC-type response regulator. Our discovery supports the idea that exploiting pro-QS molecules is a promising strategy for the development of novel anti-infectives. |
| first_indexed | 2024-12-17T20:57:46Z |
| format | Article |
| id | doaj.art-121e3c97499a4a24a44d02e64c0df70b |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-17T20:57:46Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-121e3c97499a4a24a44d02e64c0df70b2022-12-21T21:32:48ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-0186e100276710.1371/journal.ppat.1002767Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios.Wai-Leung NgLark PerezJianping CongMartin F SemmelhackBonnie L BasslerQuorum sensing (QS) is a bacterial cell-cell communication process that relies on the production and detection of extracellular signal molecules called autoinducers. QS allows bacteria to perform collective activities. Vibrio cholerae, a pathogen that causes an acute disease, uses QS to repress virulence factor production and biofilm formation. Thus, molecules that activate QS in V. cholerae have the potential to control pathogenicity in this globally important bacterium. Using a whole-cell high-throughput screen, we identified eleven molecules that activate V. cholerae QS: eight molecules are receptor agonists and three molecules are antagonists of LuxO, the central NtrC-type response regulator that controls the global V. cholerae QS cascade. The LuxO inhibitors act by an uncompetitive mechanism by binding to the pre-formed LuxO-ATP complex to inhibit ATP hydrolysis. Genetic analyses suggest that the inhibitors bind in close proximity to the Walker B motif. The inhibitors display broad-spectrum capability in activation of QS in Vibrio species that employ LuxO. To the best of our knowledge, these are the first molecules identified that inhibit the ATPase activity of a NtrC-type response regulator. Our discovery supports the idea that exploiting pro-QS molecules is a promising strategy for the development of novel anti-infectives.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761573/?tool=EBI |
| spellingShingle | Wai-Leung Ng Lark Perez Jianping Cong Martin F Semmelhack Bonnie L Bassler Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios. PLoS Pathogens |
| title | Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios. |
| title_full | Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios. |
| title_fullStr | Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios. |
| title_full_unstemmed | Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios. |
| title_short | Broad spectrum pro-quorum-sensing molecules as inhibitors of virulence in vibrios. |
| title_sort | broad spectrum pro quorum sensing molecules as inhibitors of virulence in vibrios |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761573/?tool=EBI |
| work_keys_str_mv | AT waileungng broadspectrumproquorumsensingmoleculesasinhibitorsofvirulenceinvibrios AT larkperez broadspectrumproquorumsensingmoleculesasinhibitorsofvirulenceinvibrios AT jianpingcong broadspectrumproquorumsensingmoleculesasinhibitorsofvirulenceinvibrios AT martinfsemmelhack broadspectrumproquorumsensingmoleculesasinhibitorsofvirulenceinvibrios AT bonnielbassler broadspectrumproquorumsensingmoleculesasinhibitorsofvirulenceinvibrios |