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Controlling chronic Pseudomonas aeruginosa infections by strategically interfering with the sensory function of SagS
Author(s) -
Dingemans Jozef,
AlFeghali Rebecca E.,
Lau Gee W.,
Sauer Karin
Publication year - 2019
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14215
Subject(s) - biofilm , pseudomonas aeruginosa , biology , virulence , microbiology and biotechnology , tobramycin , mutant , antibiotics , bacteria , gene , genetics
Summary The hybrid sensor SagS plays a central role in the formation of  Pseudomonas aeruginosa  biofilms, by enabling the switch from the planktonic to the biofilm mode of growth and by facilitating the transition of biofilm cells to a highly tolerant state. In this study, we examined the importance of the SagS key amino acid residues associated with biofilm formation (L154) and antibiotic tolerance (D105) in P. aeruginosa  virulence. Recombinant P. aeruginosa Δ sagS and Δ sagS chromosomally expressing wild‐type  sagS, or its two variants D105A and L154A, were tested for their potential to form biofilms and cause virulence in plants and mouse models of acute and chronic pneumonia. Although mutation of  sagS did not alter P. aeruginosa virulence during acute infections, a significant difference in pathogenicity of  sagS mutants was observed during chronic infections, with the L154A variant showing reduced bacterial loads in the chronic pneumonia model, while interference with the D105 residue enhanced the susceptibility of  P. aeruginosa biofilms during tobramycin treatment. Our findings suggest that interference with the biofilm or tolerance regulatory circuits of SagS affects  P. aeruginosa  pathogenicity in chronic but not acute infections, and reveal SagS to be a promising new target to treat  P. aeruginosa  biofilm infections.

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