scholarly journals Cis-2-dodecenoic acid quorum sensing system modulates N-acyl homoserine lactone production through RpfR and cyclic di-GMP turnover in Burkholderia cenocepacia

2013 ◽  
Vol 13 (1) ◽  
pp. 148 ◽  
Author(s):  
Yinyue Deng ◽  
Amy Lim ◽  
Jing Wang ◽  
Tielin Zhou ◽  
Shaohua Chen ◽  
...  
Microbiology ◽  
2003 ◽  
Vol 149 (12) ◽  
pp. 3649-3658 ◽  
Author(s):  
P. A. Sokol ◽  
U. Sajjan ◽  
M. B. Visser ◽  
S. Gingues ◽  
J. Forstner ◽  
...  

The cepIR genes encode an N-acyl homoserine lactone (AHL)-dependent quorum-sensing system consisting of an AHL synthase that directs the synthesis of N-octanoyl-l-homoserine lactone (ohl) and n-hexanoyl-l-homoserine lactone and a transcriptional regulator. The virulence of cepIR mutants was examined in two animal models. Rats were infected with agar beads containing Burkholderia cenocepacia K56-2, K56-I2 (cepI : : Tpr) or K56-R2 (cepR : : Tn5-OT182). At 10 days post-infection, the extent of lung histopathological changes was significantly lower in lungs infected with K56-I2 or K56-R2 compared to the parent strain. Intranasal infections were performed in Cftr (−/−) mice and their wild-type siblings. K56-2 was more virulent in both groups of mice. K56-I2 was the least virulent strain and was not invasive in the Cftr (−/−) mice. OHL was readily detected in lung homogenates from Cftr (−/−) mice infected with K56-2 but was only detected at levels slightly above background in a few mice infected with K56-I2. Lung homogenates from mice infected with K56-2 had significantly higher levels of the inflammatory mediators murine macrophage inflammatory protein-2, KC/N51, interleukin-1β and interleukin-6 than those from K56-I2-infected animals. These studies indicate that a functional CepIR quorum-sensing system contributes to the severity of B. cenocepacia infections. A zinc metalloprotease gene (zmpA) was shown to be regulated by CepR and may be one of the factors that accounts for the difference in virulence between the cepI mutant and the parent strain.


2005 ◽  
Vol 73 (8) ◽  
pp. 4982-4992 ◽  
Author(s):  
Rebecca J. Malott ◽  
Adam Baldwin ◽  
Eshwar Mahenthiralingam ◽  
Pamela A. Sokol

ABSTRACT Several transmissible Burkholderia cenocepacia strains that infect multiple cystic fibrosis patients contain a genomic island designated as the cenocepacia island (cci). The cci contains a predicted N-acylhomoserine lactone (AHL) synthase gene, cciI, and a predicted response regulator gene, cciR. AHL production profiles indicated that CciI catalyzes the synthesis of N-hexanoyl-l-homoserine lactone and minor amounts of N-octanoyl-l-homoserine lactone. The cciI and cciR genes were found to be cotranscribed by reverse transcription-PCR analysis, and the expression of a cciIR::luxCDABE fusion in a cciR mutant suggested that the cciIR system negatively regulates its own expression. B. cenocepacia strains also have a cepIR quorum-sensing system. Expression of cepI::luxCDABE or cepR::luxCDABE fusions in a cciR mutant showed that CciR negatively regulates cepI but does not regulate cepR. Expression of the cciIR::luxCDABE fusion in a cepR mutant indicated that functional CepR is required for cciIR expression. Phylogenetic analysis suggested that the cciIR system was acquired by horizontal gene transfer from a distantly related organism and subsequently incorporated into the ancestral cepIR regulatory network. Mutations in cciI, cciR, cepI cciI, and cepR cciR were constructed in B. cenocepacia K56-2. The cciI mutant had greater protease activity and less swarming motility than the parent strain. The cciR mutant had less protease activity than the parent strain. The phenotypes of the cepI cciI and cepR cciR mutants were similar to cepI or cepR mutants, with less protease activity and swarming motility than the parent strain.


2008 ◽  
Vol 190 (14) ◽  
pp. 5137-5141 ◽  
Author(s):  
Breck A. Duerkop ◽  
Jake P. Herman ◽  
Ricky L. Ulrich ◽  
Mair E. A. Churchill ◽  
E. Peter Greenberg

ABSTRACT Burkholderia mallei has two acyl-homoserine lactone (acyl-HSL) signal generator-receptor pairs and two additional signal receptors, all of which contribute to virulence. We show that B. mallei produces N-3-hydroxy-octanoyl HSL (3OHC8-HSL) but a bmaI3 mutant does not. Recombinant Escherichia coli expressing BmaI3 produces hydroxylated acyl-HSLs, with 3OHC8-HSL being the most abundant compound. In recombinant E. coli, BmaR3 responds to 3OHC8-HSL but not to other acyl-HSLs. These data indicate that the signal for BmaR3-BmaI3 quorum sensing is 3OHC8-HSL.


2016 ◽  
Vol 4 (4) ◽  
Author(s):  
Akhilandeswarre Dharmaprakash ◽  
Dinesh Reghunathan ◽  
Krishnakutty C. Sivakumar ◽  
Manoj Prasannakumar ◽  
Sabu Thomas

We report for the first time the draft genome sequence of two psychrotrophic Pseudomonas species, Pseudomonas simiae RGCB 73 and Pseudomonas brenneri RGCB 108, from the Arctic that produce more than one acyl homoserine lactone molecule of varied N -acyl length. The study confirms the presence of a LuxR-LuxI (type) mediated quorum-sensing system in both the Pseudomonas species and enables us to understand the role of quorum sensing in their survival in extremely cold environments.


2006 ◽  
Vol 4 (2) ◽  
pp. 45-54
Author(s):  
UMI LESTARI ◽  
ARTINI PANGASTUTI ◽  
ARI SUSILOWATI

Conventional treatment of infectious diseases is based on compounds that kill or inhibit the growth of bacteria. A major concern with this approach is the frequent development of resistance to antimicrobial compounds. The discovery of communication (quorum sensing system) regulating bacterial virulence opens up ways to control certain bacterial infectious without interfering the growth. The fish pathogen Aeromonas hydrophila produces quorum sensing signal, NButanoyl-L-Homoserine Lactone (C4-HSL). C4-HSL regulates exoprotease synthesis, a virulence factor of A. hydrophila. Expression of exoprotease can be blocked by using quorum sensing inhibitor. The purpose of this study was to investigate the inhibiting effect of Curcuma xanthorrhiza (Roxb.) extract to exoprotease production of A. hydrophila. Extraction was conducted by using n-hexane, ethyl acetate and ethanol. The qualitative exoprotease assay result showed that n-hexane extract of C. xanthorrhiza had not effect on growth and exoprotease production of A. hydrophila. Meanwhile, 4% of ethyl acetate and ethanol extract of C. xanthorrhiza can inhibit exoprotease production without affecting A. hydrophilla growth. The quantitative exoprotease assay result showed that 4% of ethyl acetate and ethanol extract can inhibit the exoprotease production by 93,9% and 95,6%. The growth of A. hydrophila was not affected by this extract.


2019 ◽  
Vol 85 (8) ◽  
Author(s):  
Chaoyu Cui ◽  
Shihao Song ◽  
Chunxi Yang ◽  
Xiuyun Sun ◽  
Yutong Huang ◽  
...  

ABSTRACTQuorum sensing (QS) signals are widely used by bacterial pathogens to control biological functions and virulence in response to changes in cell population densities.Burkholderia cenocepaciaemploys a molecular mechanism in which thecis-2-dodecenoic acid (namedBurkholderiadiffusiblesignalfactor [BDSF]) QS system regulatesN-acyl homoserine lactone (AHL) signal production and virulence by modulating intracellular levels of cyclic diguanosine monophosphate (c-di-GMP). Thus, inhibition of BDSF signaling may offer a non-antibiotic-based therapeutic strategy against BDSF-regulated bacterial infections. In this study, we report the synthesis of small-molecule mimics of the BDSF signal and evaluate their ability to inhibit BDSF QS signaling inB. cenocepacia. A novel structural analogue of BDSF, 14-Me-C16:Δ2(cis-14-methylpentadec-2-enoic acid), was observed to inhibit BDSF production and impair BDSF-regulated phenotypes inB. cenocepacia, including motility, biofilm formation, and virulence, while it did not inhibit the growth rate of this pathogen. 14-Me-C16:Δ2also reduced AHL signal production. Genetic and biochemical analyses showed that 14-Me-C16:Δ2inhibited the production of the BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Notably, 14-Me-C16:Δ2attenuated BDSF-regulated phenotypes in variousBurkholderiaspecies. These findings suggest that 14-Me-C16:Δ2could potentially be developed as a new therapeutic agent against pathogenicBurkholderiaspecies by interfering with their QS signaling.IMPORTANCEBurkholderia cenocepaciais an important opportunistic pathogen which can cause life-threatening infections in susceptible individuals, particularly in cystic fibrosis and immunocompromised patients. It usually employs two types of quorum sensing (QS) systems, including thecis-2-dodecenoic acid (BDSF) system andN-acyl homoserine lactone (AHL) system, to regulate virulence. In this study, we have designed and identified an unsaturated fatty acid compound (cis-14-methylpentadec-2-enoic acid [14-Me-C16:Δ2]) that is capable of interfering withB. cenocepaciaQS signaling and virulence. We demonstrate that 14-Me-C16:Δ2reduced BDSF and AHL signal production inB. cenocepacia. It also impaired QS-regulated phenotypes in variousBurkholderiaspecies. These results suggest that 14-Me-C16:Δ2could interfere with QS signaling in manyBurkholderiaspecies and might be developed as a new antibacterial agent.


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