LasRdefective

LasR-defective refers to mutations in the lasR gene of Pseudomonas aeruginosa that render the LasR transcriptional regulator nonfunctional. LasR is a central component of the bacterium's quorum-sensing network, which coordinates the expression of numerous genes in response to cell density. Defective LasR mutants exhibit altered regulation of virulence factors and other community-wide traits, affecting interactions with hosts and environments.

Genetic and biochemical basis: LasR binds the autoinducer 3-oxo-dodecanoyl-homoserine lactone produced by LasI; upon binding, LasR activates transcription of genes regulated by the Las system, including elastase (lasB) and exotoxin A, among others. Mutations in lasR disrupt this signaling, leading to reduced production of many Las-controlled factors. Some LasR-defective strains retain or rewire virulence through other quorum-sensing circuits such as RhlR and PQS, or adopt alternative metabolic strategies.

Clinical and ecological relevance: LasR-defective isolates are frequently observed in chronic P. aeruginosa infections, such as in the lungs of people with cystic fibrosis or in chronic wounds. They often show diminished protease and secondary metabolite production but can exhibit enhanced biofilm formation, altered antibiotic tolerance, and improved persistence in hostile environments. The prevalence and impact of LasR defects can influence diagnostics, treatment planning, and the evolution of pathogenic communities.

Evolution and ecology: LasR loss-of-function can be driven by social cheating dynamics, where noncontributing mutants benefit from public goods produced by LasR-active neighbors. In dense biofilms or nutrient-limited conditions, selection may favor LasR-defective phenotypes, especially when other regulatory networks compensate for LasR loss. The term LasR-defective is used in publications to describe such mutants, and its interpretation depends on the ecological and genetic context.

See also: quorum sensing; Pseudomonas aeruginosa; LasI/LasR system; RhlR.