Inflammation-like environments limit the loss of quorum sensing in Pseudomonas aeruginosa
ABSTRACT Within-host environments are complex and multidimensional, making it challenging to link the evolutionary responses of colonizing pathogens to causal selective drivers. Loss of quorum sensing (QS) via mutation of the master regulator, lasR, is a common adaptation of Pseudomonas aeruginosa d...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2025-08-01
|
| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msystems.01722-24 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849735172498391040 |
|---|---|
| author | Taoran Fu Rosanna C. T. Wright Danna R. Gifford Christopher G. Knight Michael A. Brockhurst |
| author_facet | Taoran Fu Rosanna C. T. Wright Danna R. Gifford Christopher G. Knight Michael A. Brockhurst |
| author_sort | Taoran Fu |
| collection | DOAJ |
| description | ABSTRACT Within-host environments are complex and multidimensional, making it challenging to link the evolutionary responses of colonizing pathogens to causal selective drivers. Loss of quorum sensing (QS) via mutation of the master regulator, lasR, is a common adaptation of Pseudomonas aeruginosa during chronic infections. Here, we use experimental evolution in host-mimicking media to show that loss of QS is constrained by environmental factors associated with host inflammation. Specifically, environments combining oxidative stress and abundant free amino acids limited loss of QS, whereas QS loss was rapid in the absence of oxidative stress, regardless of amino acids. Under oxidative stress, lasR mutations were contingent upon first decoupling regulation of oxidative stress responses from QS via mutations in the promoter region of the primary catalase, katA, or in the oxidative stress regulator, oxyR, enabling maintenance of oxidative stress tolerance. Together, our findings suggest that host inflammatory responses likely delay the loss of QS while colonizers undergo stepwise evolution, first adapting to survive lethal stressors before responding to other nutritional selective drivers that favor loss of QS.IMPORTANCEPseudomonas aeruginosa is a common cause of chronic infections characterized by persistent inflammation. Host inflammatory responses alter within-host environments, including by increasing levels of antimicrobial stressors and releasing free amino acids through proteolysis. Here, we show stepwise adaptation of experimental P. aeruginosa populations to inflammation-like environments, first adapting to survive lethal stress by decoupling oxidative stress responses from quorum sensing (QS), before then adapting to the nutritional conditions, delaying the loss of quorum sensing. These results highlight the power of using laboratory evolution experiments to disentangle the multidimensional selective forces driving pathogen adaptation in complex within-host environments. |
| format | Article |
| id | doaj-art-a654a44b73644e86a0a12f2ecef35a69 |
| institution | DOAJ |
| issn | 2379-5077 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj-art-a654a44b73644e86a0a12f2ecef35a692025-08-20T03:07:37ZengAmerican Society for MicrobiologymSystems2379-50772025-08-0110810.1128/msystems.01722-24Inflammation-like environments limit the loss of quorum sensing in Pseudomonas aeruginosaTaoran Fu0Rosanna C. T. Wright1Danna R. Gifford2Christopher G. Knight3Michael A. Brockhurst4Division of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, England, United KingdomDivision of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, England, United KingdomDivision of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, England, United KingdomDepartment of Earth and Environmental Sciences, School of Natural Sciences, Faculty of Science and Engineering, The University of Manchester, Manchester, England, United KingdomDivision of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, England, United KingdomABSTRACT Within-host environments are complex and multidimensional, making it challenging to link the evolutionary responses of colonizing pathogens to causal selective drivers. Loss of quorum sensing (QS) via mutation of the master regulator, lasR, is a common adaptation of Pseudomonas aeruginosa during chronic infections. Here, we use experimental evolution in host-mimicking media to show that loss of QS is constrained by environmental factors associated with host inflammation. Specifically, environments combining oxidative stress and abundant free amino acids limited loss of QS, whereas QS loss was rapid in the absence of oxidative stress, regardless of amino acids. Under oxidative stress, lasR mutations were contingent upon first decoupling regulation of oxidative stress responses from QS via mutations in the promoter region of the primary catalase, katA, or in the oxidative stress regulator, oxyR, enabling maintenance of oxidative stress tolerance. Together, our findings suggest that host inflammatory responses likely delay the loss of QS while colonizers undergo stepwise evolution, first adapting to survive lethal stressors before responding to other nutritional selective drivers that favor loss of QS.IMPORTANCEPseudomonas aeruginosa is a common cause of chronic infections characterized by persistent inflammation. Host inflammatory responses alter within-host environments, including by increasing levels of antimicrobial stressors and releasing free amino acids through proteolysis. Here, we show stepwise adaptation of experimental P. aeruginosa populations to inflammation-like environments, first adapting to survive lethal stress by decoupling oxidative stress responses from quorum sensing (QS), before then adapting to the nutritional conditions, delaying the loss of quorum sensing. These results highlight the power of using laboratory evolution experiments to disentangle the multidimensional selective forces driving pathogen adaptation in complex within-host environments.https://journals.asm.org/doi/10.1128/msystems.01722-24experimental evolutionquorum sensingchronic infectionpathogen evolutioncystic fibrosisPseudomonas aeruginosa |
| spellingShingle | Taoran Fu Rosanna C. T. Wright Danna R. Gifford Christopher G. Knight Michael A. Brockhurst Inflammation-like environments limit the loss of quorum sensing in Pseudomonas aeruginosa mSystems experimental evolution quorum sensing chronic infection pathogen evolution cystic fibrosis Pseudomonas aeruginosa |
| title | Inflammation-like environments limit the loss of quorum sensing in Pseudomonas aeruginosa |
| title_full | Inflammation-like environments limit the loss of quorum sensing in Pseudomonas aeruginosa |
| title_fullStr | Inflammation-like environments limit the loss of quorum sensing in Pseudomonas aeruginosa |
| title_full_unstemmed | Inflammation-like environments limit the loss of quorum sensing in Pseudomonas aeruginosa |
| title_short | Inflammation-like environments limit the loss of quorum sensing in Pseudomonas aeruginosa |
| title_sort | inflammation like environments limit the loss of quorum sensing in pseudomonas aeruginosa |
| topic | experimental evolution quorum sensing chronic infection pathogen evolution cystic fibrosis Pseudomonas aeruginosa |
| url | https://journals.asm.org/doi/10.1128/msystems.01722-24 |
| work_keys_str_mv | AT taoranfu inflammationlikeenvironmentslimitthelossofquorumsensinginpseudomonasaeruginosa AT rosannactwright inflammationlikeenvironmentslimitthelossofquorumsensinginpseudomonasaeruginosa AT dannargifford inflammationlikeenvironmentslimitthelossofquorumsensinginpseudomonasaeruginosa AT christophergknight inflammationlikeenvironmentslimitthelossofquorumsensinginpseudomonasaeruginosa AT michaelabrockhurst inflammationlikeenvironmentslimitthelossofquorumsensinginpseudomonasaeruginosa |