Global regulation in Pseudomonas aeruginosa: the regulatory protein AlgR2 (AlgQ) acts as a modulator of quorum sensing

2003 ◽  
Vol 154 (3) ◽  
pp. 207-213 ◽  
Author(s):  
Fouzia Ledgham ◽  
Chantal Soscia ◽  
Ananda Chakrabarty ◽  
Andrée Lazdunski ◽  
Maryline Foglino
Microbiology ◽  
2003 ◽  
Vol 149 (11) ◽  
pp. 3073-3081 ◽  
Author(s):  
Gerardo Medina ◽  
Katy Juárez ◽  
Rafael Díaz ◽  
Gloria Soberón-Chávez

The Pseudomonas aeruginosa rhlR gene encodes the transcriptional regulator RhlR which has a central role in the quorum-sensing response. Different gene products involved in bacterial pathogenesis are regulated at the transcriptional level by two quorum-sensing response systems, Las and Rhl. The expression of rhlR has been reported to be under the control of the Las system, but its transcriptional regulation has not been studied in detail. Here, the rhlR promoter region has been characterized and shown to present four different transcription start sites, two of which are included in the upstream gene (rhlB) coding region. It was found that rhlR expression is not only dependent on LasR but also on different regulatory proteins such as Vfr and RhlR itself, and also on the alternative sigma factor σ 54. It is reported that rhlR expression is partially LasR-independent under certain culture conditions and is strongly influenced by environmental factors.


2021 ◽  
Vol 8 (1) ◽  
pp. 27-33
Author(s):  
Sepideh Ghameshlouei ◽  
Nakisa Zarrabi Ahrabi ◽  
Ali Souldozi ◽  
Yasin SarveAhrabi

Background: Oxadiazoles are a group of anti-inflammatory compounds that have a wide range of activity due to their higher efficacy. Pseudomonas aeruginosa is an opportunistic pathogen and a major pathogen of nosocomial infections. This study aimed to evaluate the antibacterial and investigation of the molecular docking of new derivatives of 1, 3, 4-oxadiazole against P. aeruginosa, in vitro & in silico. Materials and Methods: Four new derivatives were synthesized and added to our previous synthetic derivatives of 1, 3, 4-oxadiazole. The antibacterial activity of all derivatives was measured based on three standard species of P. aeruginosa using inhibition zone (IZ) and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods. Then, employing the computational design of the drug by the molecular docking method, the inhibitory effect of synthetic compounds on the LasR regulatory protein of P. aeruginosa quorum sensing system was investigated, which plays an important role in regulating the expression of pathogenic genes in bacteria. Results: The chemical structures of new compounds were characterized by IR spectra and 1H-NMR. A variety of inhibitory effects were observed by the synthesized compounds – compound 4d and 4g, in particular. Also, the inhibitory effect of these two compounds on the LasR regulatory protein under the control of the quorum sensing system in P. aeruginosa was demonstrated by molecular docking. Conclusions: The results of this study showed that the two compounds containing the functional group of naphthalene and fluorophenyl have a significant effect on the inhibition of P. aeruginosa, as well as on the LasR protein of this bacterium.


2003 ◽  
Vol 185 (7) ◽  
pp. 2227-2235 ◽  
Author(s):  
Karin Heurlier ◽  
Valerie Dénervaud ◽  
Gabriella Pessi ◽  
Cornelia Reimmann ◽  
Dieter Haas

ABSTRACT In Pseudomonas aeruginosa PAO1, the expression of several virulence factors such as elastase, rhamnolipids, and hydrogen cyanide depends on quorum-sensing regulation, which involves the lasRI and rhlRI systems controlled by N-(3-oxododecanoyl)-l-homoserine lactone and N-butyryl-l-homoserine lactone, respectively, as signal molecules. In rpoN mutants lacking the transcription factor σ54, the expression of the lasR and lasI genes was elevated at low cell densities, whereas expression of the rhlR and rhlI genes was markedly enhanced throughout growth by comparison with the wild type and the complemented mutant strains. As a consequence, the rpoN mutants had elevated levels of both signal molecules and overexpressed the biosynthetic genes for elastase, rhamnolipids, and hydrogen cyanide. The quorum-sensing regulatory protein QscR was not involved in the negative control exerted by RpoN. By contrast, in an rpoN mutant, the expression of the gacA global regulatory gene was significantly increased during the entire growth cycle, whereas another global regulatory gene, vfr, was downregulated at high cell densities. In conclusion, it appears that GacA levels play an important role, probably indirectly, in the RpoN-dependent modulation of the quorum-sensing machinery of P. aeruginosa.


2001 ◽  
Vol 183 (22) ◽  
pp. 6676-6683 ◽  
Author(s):  
Gabriella Pessi ◽  
Faye Williams ◽  
Zoë Hindle ◽  
Karin Heurlier ◽  
Matthew T. G. Holden ◽  
...  

ABSTRACT Posttranscriptional control is known to contribute to the regulation of secondary metabolism and virulence determinants in certain gram-negative bacteria. Here we report the isolation of aPseudomonas aeruginosa gene which encodes a global translational regulatory protein, RsmA (regulator of secondary metabolites). Overexpression of rsmA resulted in a substantial reduction in the levels of extracellular products, including protease, elastase, and staphylolytic (LasA protease) activity as well as the PA-IL lectin, hydrogen cyanide (HCN), and the phenazine pigment pyocyanin. While inactivation of rsmAin P. aeruginosa had only minor effects on the extracellular enzymes and the PA-IL lectin, the production of HCN and pyocyanin was enhanced during the exponential phase. The influence of RsmA on N-acylhomoserine lactone-mediated quorum sensing was determined by assaying the levels ofN-(3-oxododecanoyl)homoserine lactone (3-oxo-C12-HSL) and N-butanoylhomoserine lactone (C4-HSL) produced by the rsmA mutant and thersmA-overexpressing strain. RsmA exerted a negative effect on the synthesis of both 3-oxo-C12-HSL and C4-HSL, which was confirmed by using lasI and rhlItranslational fusions. These data also highlighted the temporal expression control of the lasI gene, which was induced much earlier and to a higher level during the exponential growth phase in an rsmA mutant. To investigate whether RsmA modulates HCN production solely via quorum-sensing control, hcntranslational fusions were employed to monitor the regulation of the cyanide biosynthesis genes (hcnABC). RsmA was shown to exert an additional negative effect on cyanogenesis posttranscriptionally by acting on a region surrounding thehcnA ribosome-binding site. This suggests that, inP. aeruginosa, RsmA functions as a pleiotropic posttranscriptional regulator of secondary metabolites directly and also indirectly by modulating the quorum-sensing circuitry.


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