Novel drug targets in cell wall biosynthesis exploited by gene disruption in Pseudomonas aeruginosa.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsElamin, Ayssar A
Shuralev, Eduard A
MetadataShow full item record
AbstractFor clinicians, Pseudomonas aeruginosa is a nightmare pathogen that is one of the top three causes of opportunistic human infections. Therapy of P. aeruginosa infections is complicated due to its natural high intrinsic resistance to antibiotics. Active efflux and decreased uptake of drugs due to cell wall/membrane permeability appear to be important issues in the acquired antibiotic tolerance mechanisms. Bacterial cell wall biosynthesis enzymes have been shown to be essential for pathogenicity of Gram-negative bacteria. However, the role of these targets in virulence has not been identified in P. aeruginosa. Here, we report knockout (k.o) mutants of six cell wall biosynthesis targets (murA, PA4450; murD, PA4414; murF, PA4416; ppiB, PA1793; rmlA, PA5163; waaA, PA4988) in P. aeruginosa PAO1, and characterized these in order to find out whether these genes and their products contribute to pathogenicity and virulence of P. aeruginosa. Except waaA k.o, deletion of cell wall biosynthesis targets significantly reduced growth rate in minimal medium compared to the parent strain. The k.o mutants showed exciting changes in cell morphology and colonial architectures. Remarkably, ΔmurF cells became grossly enlarged. Moreover, the mutants were also attenuated in vivo in a mouse infection model except ΔmurF and ΔwaaA and proved to be more sensitive to macrophage-mediated killing than the wild-type strain. Interestingly, the deletion of the murA gene resulted in loss of virulence activity in mice, and the virulence was restored in a plant model by unknown mechanism. This study demonstrates that cell wall targets contribute significantly to intracellular survival, in vivo growth, and pathogenesis of P. aeruginosa. In conclusion, these findings establish a link between cell wall targets and virulence of P. aeruginosa and thus may lead to development of novel drugs for the treatment of P. aeruginosa infection.
CitationNovel drug targets in cell wall biosynthesis exploited by gene disruption in Pseudomonas aeruginosa. 2017, 12 (10):e0186801 PLoS ONE
AffiliationHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany.
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- A Genetic Screen Reveals Novel Targets to Render <i>Pseudomonas aeruginosa</i> Sensitive to Lysozyme and Cell Wall-Targeting Antibiotics.
- Authors: Lee KM, Lee K, Go J, Park IH, Shin JS, Choi JY, Kim HJ, Yoon SS
- Issue date: 2017
- Genes from pUM505 plasmid contribute to Pseudomonas aeruginosa virulence.
- Authors: Rodríguez-Andrade E, Hernández-Ramírez KC, Díaz-Peréz SP, Díaz-Magaña A, Chávez-Moctezuma MP, Meza-Carmen V, Ortíz-Alvarado R, Cervantes C, Ramírez-Díaz MI
- Issue date: 2016 Mar
- The MexGHI-OpmD multidrug efflux pump controls growth, antibiotic susceptibility and virulence in Pseudomonas aeruginosa via 4-quinolone-dependent cell-to-cell communication.
- Authors: Aendekerk S, Diggle SP, Song Z, Høiby N, Cornelis P, Williams P, Cámara M
- Issue date: 2005 Apr
- A Macrophage Subversion Factor Is Shared by Intracellular and Extracellular Pathogens.
- Authors: Belon C, Soscia C, Bernut A, Laubier A, Bleves S, Blanc-Potard AB
- Issue date: 2015 Jun
- Community surveillance enhances Pseudomonas aeruginosa virulence during polymicrobial infection.
- Authors: Korgaonkar A, Trivedi U, Rumbaugh KP, Whiteley M
- Issue date: 2013 Jan 15