genomic sequencing of modified Pseudomonas aerug­i­nosa strains. Transcription-associated mutation of lasR in Pseudomonas aeruginosa

Pseudomonas aerug­i­nosa is an op­por­tunis­tic pathogen which infects cys­tic fi­bro­sis and can­cer pa­tients with com­pro­mised immune sys­tems. LasR is a mas­ter reg­u­la­tor which con­trols the viru­lence of P. aerug­i­nosa in re­sponse to bac­te­r­ial cell-density and host sig­nals. Dur­ing in­fec­tion, lasR is frequently mu­tated, con­fer­ring P. aerug­i­nosa a growth ad­van­tage in hosts and enhances re­sis­tance to widely used an­tibi­otics. How­ever, the mecha­nis­tic ba­sis of lasR mu­ta­tion is not well under­stood. We have tested here the hy­poth­e­sis that transcription strength is a contrib­u­tory de­ter­mi­nant of lasR mu­ta­gen­e­sis. P. aerug­i­nosa strains with dif­fer­ent lasR tran­scription strengths were therefore en­gi­neered and the lasR mu­ta­tions were mon­i­tored unbiasedly us­ing next-gen­er­a­tion se­quenc­ing technol­ogy.