Investigation Of Contingent Mutations In The Rets-gacas Regulatory System In Clinical Pseudomonas Aeruginosa Isolates From Cystic Fibrosis Patients

Mikkel Lindegaard, Rasmus Marvig, Søren Molin, Helle Krogh Johansen, Katherine Long

Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsResearchpeer-review


Introduction: Pseudomonas aeruginosa is a major pathogen infecting the airways of cystic fibrosis (CF) patients. From a collection of 474 full-genome sequenced P. aeruginosa isolates from 34 young CF patients, we have discovered parallel evolution in the RetS-GacAS regulatory system2, a key factor in the reciprocal regulation of acute and chronic infection genes. Mutations in this system occur in a sequential manner, such that mutations in retS precede mutations in gacS/gacA. Methods: Using genomics, transcriptomics, and metabolomics (Biolog), we have investigated the effects of these mutations in seven clinical isolates from two patients with two distinct clone types of P. aeruginosa. Results: Mutations in the RetS-GacAS regulatory system have a major effect on the behavior of P. aeruginosa. Initially, mutations in retS cause a shift towards aggregation/biofilm formation, type VI secretion, and phenazine production. Later, mutations in gacA/gacS cause a reciprocal shift by increasing expression type III secretion and motility genes, while decreasing expression of the former. Addtionally, Biolog data show clone type specific shifts in carbon source utilization, where one clone type expands and the other decreases the metabolic repertoires. Conclusions: The sequential nature of the mutations in the RetS-GacAS regulatory system suggests that different behavioral patterns are needed at different times of infection, where the initial mutation in retS results in a defensive behavior, enabling establishment of infection. This is then offset by mutations in gacA/gacS leading to a more expansive phenotype by dissemination of the infection.
Original languageEnglish
Title of host publicationThe Danish Microbiological Society Annual Congress 2015 : Programme & Abstracts
Place of PublicationCopenhagen
Publication date2015
Publication statusPublished - 2015
EventThe Danish Microbiological Society Annual Congress 2015 - Eigtved's Pakhus, Copenhagen, Denmark
Duration: 9 Nov 20159 Nov 2015


ConferenceThe Danish Microbiological Society Annual Congress 2015
LocationEigtved's Pakhus


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