Controlling chronic Pseudomonas aeruginosa infections by strategically interfering with the sensory function of SagS.
Mol Microbiol
; 111(5): 1211-1228, 2019 05.
Article
en En
| MEDLINE
| ID: mdl-30710463
ABSTRACT
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 ΔsagS and ΔsagS 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Pseudomonas aeruginosa
/
Infecciones por Pseudomonas
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Proteínas Bacterianas
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Neumonía Bacteriana
/
Biopelículas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Microbiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MICROBIOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos