biostudies-literatureGuadarrama-Orozco KDSECIHTIFEDERDGAPA, UNAMfiaf106https://www.ebi.ac.uk/biostudies/studies/S-EPMC12574336biostudies-literatureUnknown101(11)Pseudomonas aeruginosa is a model organism for studying social behaviors in bacteria, such as the exploitation of exoprotease by social cheaters. The current paradigm holds that continuous culture of exoprotease-producing individuals with protein as the sole carbon source selects for exoprotease non-producers mutants with an impaired quorum-sensing regulator, LasR, which controls exoprotease expression. However, recent studies reveal that some isolates lacking functional LasR still produce exoproteases under the control of another regulator, RhlR. Here, we extended this study to two clinical strains, AUS 411 and AUS 531, isolated from cystic fibrosis patients and harboring functional LasR. Surprisingly, in AUS 411, exoprotease-non-producers appeared from the first growth passage, but most FEMS microbiology ecologyChallenging the paradigm: non-canonical exoprotease cheating in clinical Pseudomonas aeruginosa isolates.PMC12574336CBF-2025-I-2121IN200224Oliver ALucero-Gil MGCadet FValdez AEsquivel-Hernandez DAGarcia-Contreras RCocotl-Yanez MPena-Ocana BAEstrada-Velasco AYIslas-Tolentino MACeapa CDFabian Del Olmo MJHusain FMGarcia-Reyes SKidd TJWood TKOlvera-Falfan LPKirigo JArshad MCanton RMaeda TMarroquin-Mendiola DLKhan AFontaine NGuadarrama-Orozco KDTomas MQuezada HFranco BToya SfalseChallenging the paradigm: non-canonical exoprotease cheating in clinical Pseudomonas aeruginosa isolates.Pseudomonas aeruginosa is a model organism for studying social behaviors in bacteria, such as the exploitation of exoprotease by social cheaters. The current paradigm holds that continuous culture of exoprotease-producing individuals with protein as the sole carbon source selects for exoprotease non-producers mutants with an impaired quorum-sensing regulator, LasR, which controls exoprotease expression. However, recent studies reveal that some isolates lacking functional LasR still produce exoproteases under the control of another regulator, RhlR. Here, we extended this study to two clinical strains, AUS 411 and AUS 531, isolated from cystic fibrosis patients and harboring functional LasR. Surprisingly, in AUS 411, exoprotease-non-producers appeared from the first growth passage, but most 2025-01-01T00:00:00Z2025 Oct2026-07-05T03:17:15.288Z2026-07-05T03:08:21.23ZS-EPMC125743364112404110.1093/femsec/fiaf106