scholarly journals Screening of Bacterial Quorum Sensing Inhibitors in a Vibrio fischeri LuxR-Based Synthetic Fluorescent E. coli Biosensor

2020 ◽  
Vol 13 (9) ◽  
pp. 263
Author(s):  
Xiaofei Qin ◽  
Celina Vila-Sanjurjo ◽  
Ratna Singh ◽  
Bodo Philipp ◽  
Francisco M. Goycoolea

A library of 23 pure compounds of varying structural and chemical characteristics was screened for their quorum sensing (QS) inhibition activity using a synthetic fluorescent Escherichia coli biosensor that incorporates a modified version of lux regulon of Vibrio fischeri. Four such compounds exhibited QS inhibition activity without compromising bacterial growth, namely, phenazine carboxylic acid (PCA), 2-heptyl-3-hydroxy-4-quinolone (PQS), 1H-2-methyl-4-quinolone (MOQ) and genipin. When applied at 50 µM, these compounds reduced the QS response of the biosensor to 33.7% ± 2.6%, 43.1% ± 2.7%, 62.2% ± 6.3% and 43.3% ± 1.2%, respectively. A series of compounds only showed activity when tested at higher concentrations. This was the case of caffeine, which, when applied at 1 mM, reduced the QS to 47% ± 4.2%. In turn, capsaicin, caffeic acid phenethyl ester (CAPE), furanone and polygodial exhibited antibacterial activity when applied at 1mM, and reduced the bacterial growth by 12.8% ± 10.1%, 24.4% ± 7.0%, 91.4% ± 7.4% and 97.5% ± 3.8%, respectively. Similarly, we confirmed that trans-cinnamaldehyde and vanillin, when tested at 1 mM, reduced the QS response to 68.3% ± 4.9% and 27.1% ± 7.4%, respectively, though at the expense of concomitantly reducing cell growth by 18.6% ± 2.5% and 16% ± 2.2%, respectively. Two QS natural compounds of Pseudomonas aeruginosa, namely PQS and PCA, and the related, synthetic compounds MOQ, 1H-3-hydroxyl-4-quinolone (HOQ) and 1H-2-methyl-3-hydroxyl-4-quinolone (MHOQ) were used in molecular docking studies with the binding domain of the QS receptor TraR as a target. We offer here a general interpretation of structure-function relationships in this class of compounds that underpins their potential application as alternatives to antibiotics in controlling bacterial virulence.

2017 ◽  
Vol 149 ◽  
pp. 358-368 ◽  
Author(s):  
Xiaofei Qin ◽  
Christoph Engwer ◽  
Saaketh Desai ◽  
Celina Vila-Sanjurjo ◽  
Francisco M. Goycoolea

2017 ◽  
Vol 15 (27) ◽  
pp. 5743-5755 ◽  
Author(s):  
Shashidhar Nizalapur ◽  
Onder Kimyon ◽  
Eugene Yee ◽  
Mohan M. Bhadbhade ◽  
Mike Manefield ◽  
...  

Novel acyclic and cyclic glyoxamides that inhibited quorum sensing mechanism and biofilm formation in Gram-negative bacteria such as P. aeruginosa and E. coli.


2007 ◽  
Vol 74 (2) ◽  
pp. 437-445 ◽  
Author(s):  
Eric L. Haseltine ◽  
Frances H. Arnold

ABSTRACT Bacteria employ quorum sensing, a form of cell-cell communication, to sense changes in population density and regulate gene expression accordingly. This work investigated the rewiring of one quorum-sensing module, the lux circuit from the marine bacterium Vibrio fischeri. Steady-state experiments demonstrate that rewiring the network architecture of this module can yield graded, threshold, and bistable gene expression as predicted by a mathematical model. The experiments also show that the native lux operon is most consistent with a threshold, as opposed to a bistable, response. Each of the rewired networks yielded functional population sensors at biologically relevant conditions, suggesting that this operon is particularly robust. These findings (i) permit prediction of the behaviors of quorum-sensing operons in bacterial pathogens and (ii) facilitate forward engineering of synthetic gene circuits.


2016 ◽  
Vol 8 ◽  
pp. PMC.S13209 ◽  
Author(s):  
Kerstin Reuter ◽  
Anke Steinbach ◽  
Volkhard Helms

Quorum sensing (QS) describes the exchange of chemical signals in bacterial populations to adjust the bacterial phenotypes according to the density of bacterial cells. This serves to express phenotypes that are advantageous for the group and ensure bacterial survival. To do so, bacterial cells synthesize autoinducer (AI) molecules, release them to the environment, and take them up. Thereby, the AI concentration reflects the cell density. When the AI concentration exceeds a critical threshold in the cells, the AI may activate the expression of virulence-associated genes or of luminescent proteins. It has been argued that targeting the QS system puts less selective pressure on these pathogens and should avoid the development of resistant bacteria. Therefore, the molecular components of QS systems have been suggested as promising targets for developing new anti-infective compounds. Here, we review the QS systems of selected gram-negative and gram-positive bacteria, namely, Vibrio fischeri, Pseudomonas aeruginosa, and Staphylococcus aureus, and discuss various antivirulence strategies based on blocking different components of the QS machinery.


2008 ◽  
Vol 21 (9) ◽  
pp. 1184-1192 ◽  
Author(s):  
Sathish Rajamani ◽  
Wolfgang D. Bauer ◽  
Jayne B. Robinson ◽  
John M. Farrow ◽  
Everett C. Pesci ◽  
...  

Many bacteria use quorum sensing (QS) as an intercellular signaling mechanism to regulate gene expression in local populations. Plant and algal hosts, in turn, secrete compounds that mimic bacterial QS signals, allowing these hosts to manipulate QS-regulated gene expression in bacteria. Lumichrome, a derivative of the vitamin riboflavin, was purified and chemically identified from culture filtrates of the alga Chlamydomonas as a QS signal-mimic compound capable of stimulating the Pseudomonas aeruginosa LasR QS receptor. LasR normally recognizes the N-acyl homoserine lactone (AHL) signal, N-3-oxo-dodecanoyl homoserine lactone. Authentic lumichrome and riboflavin stimulated the LasR receptor in bioassays and lumichrome activated LasR in gel shift experiments. Amino acid substitutions in LasR residues required for AHL binding altered responses to both AHLs and lumichrome or riboflavin. These results and docking studies indicate that the AHL binding pocket of LasR recognizes both AHLs and the structurally dissimilar lumichrome or riboflavin. Bacteria, plants, and algae commonly secrete riboflavin or lumichrome, raising the possibility that these compounds could serve as either QS signals or as interkingdom signal mimics capable of manipulating QS in bacteria with a LasR-like receptor.


mBio ◽  
2021 ◽  
Author(s):  
T. Essock-Burns ◽  
B. D. Bennett ◽  
D. Arencibia ◽  
S. Moriano-Gutierrez ◽  
M. Medeiros ◽  
...  

Interbacterial signaling within a host-associated population can have profound effects on the behavior of the bacteria, for instance, in their production of virulence/colonization factors; in addition, such signaling can dictate the nature of the outcome for the host, in both pathogenic and beneficial associations. Using the monospecific squid-vibrio model of symbiosis, we examined how quorum-sensing regulation by the Vibrio fischeri population induces a biogeographic tissue phenotype that promotes the retention of this extracellular symbiont within the light organ of its host, Euprymna scolopes .


2021 ◽  
Vol 12 ◽  
Author(s):  
Yuki Hoshiko ◽  
Yoshito Nishiyama ◽  
Tae Moriya ◽  
Kiwao Kadokami ◽  
Luis Esaú López-Jácome ◽  
...  

Bdellovibrio bacteriovorus is one of the predatory bacteria; therefore, it can act as a novel “living antibiotic,” unlike the current antibiotics. Here the predation of Escherichia coli by B. bacteriovorus was inhibited in the presence of Pseudomonas aeruginosa. This study investigated whether P. aeruginosa-induced predation inhibition is associated with bacterial quorum sensing (QS). Each las, rhl, or pqs QS mutant in P. aeruginosa was used to check the predatory activity of E. coli cells using B. bacteriovorus. As a result, the predatory activity of B. bacteriovorus increased in a mutant pqs QS system, whereas wild-type PA14 inhibited the predatory activity. Moreover, the addition of 4-hydroxy-2-heptylquinoline (HHQ) or the analog triggered the low predatory activity of B. bacteriovorus and killed B. bacteriovorus cells. Therefore, a defensive action of P. aeruginosa against B. bacteriovorus is activated by the pqs QS system, which produces some quinolone compounds such as HHQ.


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