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Transcriptome Analysis Reveals That the RNA Polymerase-Binding Protein DksA1 Has Pleiotropic Functions in Pseudomonas aeruginosa

Authors
 Kyung Bae Min  ;  Sang Sun Yoon 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.295(12) : 3851-3864, 2020-03 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2020-03
Keywords
DksA1 ; Pseudomonas aeruginosa ; anaerobic respiration ; gene regulation ; polyamine metabolism ; quorum sensing ; stress response ; stringent response ; transcription factor ; transcription regulation ; virulence factor
Abstract
The stringent response (SR) is a highly conserved stress response in bacteria. It is composed of two factors, (i) a nucleotide alarmone, guanosine tetra- and pentaphosphate ((p)ppGpp), and (ii) an RNA polymerase-binding protein, DksA, that regulates various phenotypes, including bacterial virulence. The clinically significant opportunistic bacterial pathogen Pseudomonas aeruginosa possesses two genes, dksA1 and dksA2, that encode DksA proteins. It remains elusive, however, which of these two genes plays a more important role in SR regulation. In this work, we compared genome-wide, RNA-Seq-based transcriptome profiles of ΔdksA1, ΔdksA2, and ΔdksA1ΔdksA2 mutants to globally assess the effects of these gene deletions on transcript levels coupled with phenotypic analyses. The ΔdksA1 mutant exhibited substantial defects in a wide range of phenotypes, including quorum sensing (QS), anaerobiosis, and motility, whereas the ΔdksA2 mutant exhibited no significant phenotypic changes, suggesting that the dksA2 gene may not have an essential function in P. aeruginosa under the conditions used here. Of note, the ΔdksA1 mutants displayed substantially increased transcription of genes involved in polyamine biosynthesis, and we also detected increased polyamine levels in these mutants. Because SAM is a shared precursor for the production of both QS autoinducers and polyamines, these findings suggest that DksA1 deficiency skews the flow of SAM toward polyamine production rather than to QS signaling. Together, our results indicate that DksA1, but not DksA2, controls many important phenotypes in P. aeruginosa We conclude that DksA1 may represent a potential target whose inhibition may help manage recalcitrant P. aeruginosa infections.
Full Text
https://www.jbc.org/content/295/12/3851.long
DOI
10.1074/jbc.RA119.011692
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Sang Sun(윤상선) ORCID logo https://orcid.org/0000-0003-2979-365X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/175962
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