Lasi

LasI is an autoinducer synthase in the Las quorum sensing system of the bacterium Pseudomonas aeruginosa. It belongs to the LuxI family of AHL synthases and catalyzes the production of the signaling molecule N-(3-oxo-dodecanoyl)-L-homoserine lactone (3OC12-HSL). The enzyme uses acyl-ACP as the acyl donor and S-adenosyl-L-methionine (SAM) as a co-substrate to generate 3OC12-HSL, which freely diffuses across the cell envelope.

Once the concentration of 3OC12-HSL reaches a threshold, it binds LasR, a transcriptional regulator, forming a complex that activates transcription of lasI and a broad set of virulence genes, establishing a positive feedback loop that strengthens quorum sensing.

LasI sits at the top of the hierarchy in the P. aeruginosa quorum-sensing network, often coordinating the activity of the Rhl system (RhlI/RhlR) and modulating virulence factor production, biofilm development, and host interactions. The Las system thereby coordinates the expression of elastase, proteases, pigments, and other traits relevant to pathogenicity and environmental adaptation.

In research and medicine, LasI and its signaling pathway are studied as targets for anti-virulence strategies aimed at attenuating infections by disarming virulence rather than killing the bacteria. Inhibitors targeting LasI synthesis or LasR signaling have been explored to reduce pathogenicity and biofilm formation in P. aeruginosa infections. LuxI-family synthases, including LasI, illustrate a conserved mechanism of AHL-based communication across various Gram-negative bacteria.