Evolution of PqsE as a Pseudomonas aeruginosa-specific regulator of LuxR-type receptors: insights from Pseudomonas and Burkholderia
ABSTRACT Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that poses a significant public health threat, particularly in healthcare settings. A key determinant of P. aeruginosa virulence is the regulated synthesis and release of extracellular products, which is controlled by a cell d...
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American Society for Microbiology
2025-05-01
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.00646-25 |
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| author | Caleb P. Mallery Kayla A. Simanek Autumn N. Pope Jon E. Paczkowski |
| author_facet | Caleb P. Mallery Kayla A. Simanek Autumn N. Pope Jon E. Paczkowski |
| author_sort | Caleb P. Mallery |
| collection | DOAJ |
| description | ABSTRACT Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that poses a significant public health threat, particularly in healthcare settings. A key determinant of P. aeruginosa virulence is the regulated synthesis and release of extracellular products, which is controlled by a cell density-dependent signaling system known as quorum sensing (QS). P. aeruginosa uses a complex QS network, including two systems that rely on diffusible N-acylhomoserine lactone (AHL) signal molecules. The LuxR-type receptor RhlR is unique in that it requires not only its cognate AHL but also the accessory protein PqsE to maximally bind to promoter DNA and initiate transcription. Our group previously demonstrated that PqsE physically interacts with RhlR, enhancing its affinity for target promoters across the P. aeruginosa genome. Although LuxR-type receptors are widespread in Gram-negative bacteria and important for pathogenesis, PqsE orthologs are restricted to Pseudomonas and Burkholderia species. This study explored the conservation of PqsE and examined PqsE ortholog structure-function across different species. Our results show that PqsE in Pseudomonas retains their functional interactions with RhlR homologs, unlike PqsE orthologs in Burkholderia spp., which do not interact with their respective LuxR-type receptors. Additionally, we assessed the AHL preferences of different receptors and hypothesized that the PqsE-RhlR interaction evolved to stabilize the inherently unstable RhlR, preventing its degradation. Indeed, we observe higher levels of RhlR protein turnover in a strain lacking pqsE compared to a wild-type strain of PA14, which can be partially rescued in a strain of P. aeruginosa lacking the Lon protease.IMPORTANCEPseudomonas aeruginosa, a major pathogen for patients with cystic fibrosis and a primary constituent of healthcare-associated infections, relies on a complex quorum-sensing (QS) network to coordinate virulence factor production. Central to this system is the interaction between two proteins, PqsE and RhlR, which drive gene expression essential for pathogenesis. Our study investigates the conservation of the PqsE-RhlR interaction across related bacterial species, revealing that PqsE in Pseudomonas can enhance RhlR activity, while orthologs in Burkholderia lack this capacity. These findings offer new insights into the specificity and evolution of QS mechanisms, highlighting the PqsE-RhlR interaction as a potentially selective target for treating P. aeruginosa infections. |
| format | Article |
| id | doaj-art-63438d2d06d94b3bb74357ebb90d759e |
| institution | OA Journals |
| issn | 2150-7511 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | American Society for Microbiology |
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| series | mBio |
| spelling | doaj-art-63438d2d06d94b3bb74357ebb90d759e2025-08-20T01:50:45ZengAmerican Society for MicrobiologymBio2150-75112025-05-0116510.1128/mbio.00646-25Evolution of PqsE as a Pseudomonas aeruginosa-specific regulator of LuxR-type receptors: insights from Pseudomonas and BurkholderiaCaleb P. Mallery0Kayla A. Simanek1Autumn N. Pope2Jon E. Paczkowski3Department of Biomedical Sciences, College of Integrated Health Sciences, University at Albany, Albany, New York, USADepartment of Biomedical Sciences, College of Integrated Health Sciences, University at Albany, Albany, New York, USADivision of Genetics, New York State Department of Health, Wadsworth Center, Albany, New York, USADepartment of Biomedical Sciences, College of Integrated Health Sciences, University at Albany, Albany, New York, USAABSTRACT Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that poses a significant public health threat, particularly in healthcare settings. A key determinant of P. aeruginosa virulence is the regulated synthesis and release of extracellular products, which is controlled by a cell density-dependent signaling system known as quorum sensing (QS). P. aeruginosa uses a complex QS network, including two systems that rely on diffusible N-acylhomoserine lactone (AHL) signal molecules. The LuxR-type receptor RhlR is unique in that it requires not only its cognate AHL but also the accessory protein PqsE to maximally bind to promoter DNA and initiate transcription. Our group previously demonstrated that PqsE physically interacts with RhlR, enhancing its affinity for target promoters across the P. aeruginosa genome. Although LuxR-type receptors are widespread in Gram-negative bacteria and important for pathogenesis, PqsE orthologs are restricted to Pseudomonas and Burkholderia species. This study explored the conservation of PqsE and examined PqsE ortholog structure-function across different species. Our results show that PqsE in Pseudomonas retains their functional interactions with RhlR homologs, unlike PqsE orthologs in Burkholderia spp., which do not interact with their respective LuxR-type receptors. Additionally, we assessed the AHL preferences of different receptors and hypothesized that the PqsE-RhlR interaction evolved to stabilize the inherently unstable RhlR, preventing its degradation. Indeed, we observe higher levels of RhlR protein turnover in a strain lacking pqsE compared to a wild-type strain of PA14, which can be partially rescued in a strain of P. aeruginosa lacking the Lon protease.IMPORTANCEPseudomonas aeruginosa, a major pathogen for patients with cystic fibrosis and a primary constituent of healthcare-associated infections, relies on a complex quorum-sensing (QS) network to coordinate virulence factor production. Central to this system is the interaction between two proteins, PqsE and RhlR, which drive gene expression essential for pathogenesis. Our study investigates the conservation of the PqsE-RhlR interaction across related bacterial species, revealing that PqsE in Pseudomonas can enhance RhlR activity, while orthologs in Burkholderia lack this capacity. These findings offer new insights into the specificity and evolution of QS mechanisms, highlighting the PqsE-RhlR interaction as a potentially selective target for treating P. aeruginosa infections.https://journals.asm.org/doi/10.1128/mbio.00646-25quorum sensingevolutionary biologytranscriptional regulationprotein-protein interactionsproteasome |
| spellingShingle | Caleb P. Mallery Kayla A. Simanek Autumn N. Pope Jon E. Paczkowski Evolution of PqsE as a Pseudomonas aeruginosa-specific regulator of LuxR-type receptors: insights from Pseudomonas and Burkholderia mBio quorum sensing evolutionary biology transcriptional regulation protein-protein interactions proteasome |
| title | Evolution of PqsE as a Pseudomonas aeruginosa-specific regulator of LuxR-type receptors: insights from Pseudomonas and Burkholderia |
| title_full | Evolution of PqsE as a Pseudomonas aeruginosa-specific regulator of LuxR-type receptors: insights from Pseudomonas and Burkholderia |
| title_fullStr | Evolution of PqsE as a Pseudomonas aeruginosa-specific regulator of LuxR-type receptors: insights from Pseudomonas and Burkholderia |
| title_full_unstemmed | Evolution of PqsE as a Pseudomonas aeruginosa-specific regulator of LuxR-type receptors: insights from Pseudomonas and Burkholderia |
| title_short | Evolution of PqsE as a Pseudomonas aeruginosa-specific regulator of LuxR-type receptors: insights from Pseudomonas and Burkholderia |
| title_sort | evolution of pqse as a pseudomonas aeruginosa specific regulator of luxr type receptors insights from pseudomonas and burkholderia |
| topic | quorum sensing evolutionary biology transcriptional regulation protein-protein interactions proteasome |
| url | https://journals.asm.org/doi/10.1128/mbio.00646-25 |
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