scholarly journals Targeting Acyl Homoserine Lactone (AHL) of Pseudomonas aeruginosa Responsible for Biofilm Formation using Plant Metabolites

2019 ◽  
Vol 13 (3) ◽  
pp. 1841-1846
Author(s):  
Sree Samanvitha K ◽  
Sanjay Kumar S ◽  
Antony V. Samrot ◽  
Raji P ◽  
Ponnaiah Paulraj ◽  
...  
2015 ◽  
Vol 5 (1) ◽  
Author(s):  
O. Lidor ◽  
A. Al-Quntar ◽  
E. C. Pesci ◽  
D. Steinberg

Abstract Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen responsible for many human infections. LasI is an acyl-homoserine lactone synthase that produces a quorum-sensing (QS) signal that positively regulates numerous P. aeruginosa virulence determinants. The inhibition of the LasI protein is therefore an attractive drug target. In this study, a novel in silico to in vitro complementation was applied to screen thiazolidinedione-type compounds for their ability to inhibit biofilm formation at concentrations not affecting bacterial growth. The compound (z)-5-octylidenethiazolidine-2, 4-dione (TZD-C8) was a strong inhibitor of biofilm formation and chosen for further study. Structural exploration of in silico docking predicted that the compound had high affinity for the LasI activity pocket. The TZD-C8 compound was also predicted to create hydrogen bonds with residues Arg30 and Ile107. Site-directed mutagenesis (SDM) of these two sites demonstrated that TZD-C8 inhibition was abolished in the lasI double mutant PAO-R30D, I107S. In addition, in vitro swarming motility and quorum sensing signal production were affected by TZD-C 8, confirming this compound alters the cell to cell signalling circuitry. Overall, this novel inhibitor of P. aeruginosa quorum sensing shows great promise and validates our mechanistic approach to discovering inhibitors of LuxI-type acyl-homoserine lactone synthases.


2019 ◽  
Vol 82 (3) ◽  
pp. 379-389 ◽  
Author(s):  
ZAIXIANG LOU ◽  
KEKGABILE S. LETSIDIDI ◽  
FUHAO YU ◽  
ZEJUN PEI ◽  
HONGXIN WANG ◽  
...  

ABSTRACT The aim of the present study was to evaluate the quorum sensing (QS) inhibition potential of eugenol and eugenol nanoemulsion against QS-dependent virulence factor production and gene expression, as well as biofilm formation in Pseudomonas aeruginosa. In the current study, eugenol nanoemulsion at a sub-MIC of 0.2 mg/mL specifically inhibited about 50% of the QS-mediated violacein production in Chromobacterium violaceum, as well as the production of N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) and C4-HSL N-acyl homoserine lactone signal molecules, pyocyanin, and swarming motility in P. aeruginosa. The inhibitive effect of eugenol and its nanoemulsion on the expression of the QS synthase genes was concentration dependent, displaying 65 and 52% expression level for lasI, respectively, and 61 and 45% expression level for rhlI, respectively, at a concentration of 0.2 mg/mL. In addition, the inhibitive effect of eugenol and its nanoemulsion on the expression of the rhlA gene responsible for the production of rhamnolipid was also concentration dependent, displaying 65 and 51% expression level for the rhlA gene, respectively, at a concentration of 0.2 mg/mL. Eugenol and its nanoemulsion also displayed 36 and 63% respective inhibition of biofilm formation by P. aeruginosa at the 0.2 mg/mL concentration. Therefore, the nanoemulsion could be used as a novel QS-based antibacterial and antibiofilm agent for the control of harmful bacteria.


2013 ◽  
Vol 825 ◽  
pp. 107-110
Author(s):  
Sören Bellenberg ◽  
Robert Barthen ◽  
Mario Vera ◽  
Nicolas Guiliani ◽  
Wolfgang Sand

A functional luxIR-type Quorum Sensing (QS) system is present in Acidithiobacillus ferrooxidans. However, cell-cell communication among various acidophilic chemolithoautotrophs growing on pyrite has not been studied in detail. These aspects are the scope of this study with emphasis on the effects exerted by the N-acyl-homoserine lactone (AHL) type signaling molecules which are produced by Acidithiobacillus ferrooxidans. Their effects on attachment and leaching efficiency by other leaching bacteria, such as Acidithiobacillus ferrivorans, Acidiferrobacter spp. SPIII/3 and Leptospirillum ferrooxidans in pure and mixed cultures growing on pyrite is shown.


2013 ◽  
Vol 76 (2) ◽  
pp. 239-247 ◽  
Author(s):  
IQBAL KABIR JAHID ◽  
NA-YOUNG LEE ◽  
ANNA KIM ◽  
SANG-DO HA

Aeromonas hydrophila recently has received increased attention because it is opportunistic and a primary human pathogen. A. hydrophila biofilm formation and its control are a major concern for food safety because biofilms are related to virulence. Therefore, we investigated biofilm formation, motility inhibition, quorum sensing, and exoprotease production of this opportunistic pathogen in response to various glucose concentrations from 0.05 to 2.5% (wt/vol). More than 0.05% glucose significantly impaired (P < 0.05) quorum sensing, biofilm formation, protease production, and swarming and swimming motility, whereas bacteria treated with 0.05% glucose had activity similar to that of the control (0% glucose). A stage shift biofilm assay revealed that the addition of glucose (2.5%) inhibited initial biofilm formation but not later stages. However, addition of quorum sensing molecules N-3-butanoyl-DL-homoserine lactone and N-3-hexanoyl homoserine lactone partially restored protease production, indicating that quorum sensing is controlled by glucose concentrations. Thus, glucose present in food or added as a preservative could regulate acyl-homoserine lactone quorum sensing molecules, which mediate biofilm formation and virulence in A. hydrophila.


2006 ◽  
Vol 73 (2) ◽  
pp. 650-654 ◽  
Author(s):  
Christophe Dubuis ◽  
Dieter Haas

ABSTRACT Signal extracts prepared from culture supernatants of Pseudomonas fluorescens CHA0 and Pseudomonas aeruginosa PAO stimulated GacA-dependent expression of small RNAs and hence of antibiotic compounds in both hosts. Pseudomonas corrugata LMG2172 and P. fluorescens SBW25 also produced signal molecules stimulating GacA-controlled antibiotic synthesis in strain CHA0, illustrating a novel, N-acyl-homoserine lactone-independent type of interspecies communication.


Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 499 ◽  
Author(s):  
Bao Zhang ◽  
Xiyi Zhuang ◽  
Liyun Guo ◽  
Robert J. C. McLean ◽  
Weihua Chu

Quorum quenching (QQ) is a promising alternative infection-control strategy to antibiotics that controls quorum-regulated virulence without killing the pathogens. Aeromonas hydrophila is an opportunistic gram-negative pathogen living in freshwater and marine environments. A. hydrophila possesses an N-acyl homoserine lactone (AHL)-based quorum-sensing (QS) system that regulates virulence, so quorum signal-inactivation (i.e., QQ) may represent a new way to combat A. hydrophila infection. In this study, an AHL lactonase gene, aiiA was cloned from Bacillus sp. strain QSI-1 and expressed in Escherichia coli strain BL21(DE3). The A. hydrophila hexanoyl homoserine lactone (C6-HSL) QS signal molecule was degraded by AiiAQSI-1, which resulted in a decrease of bacterial swimming motility, reduction of extracellular protease and hemolysin virulence factors, and inhibited the biofilm formation of A. hydrophila YJ-1 in a microtiter assay. In cell culture studies, AiiAQSI-1 decreased the ability of A. hydrophila adherence to and internalization by Epithelioma papulosum cyprini (EPC) cells. During in vivo studies, oral administration of AiiAQSI-1 via feed supplementation attenuated A. hydrophila infection in Crucian Carp. Results from this work indicate that feed supplementation with AiiAQSI-1 protein has potential to control A. hydrophila aquaculture disease via QQ.


2001 ◽  
Vol 67 (4) ◽  
pp. 1865-1873 ◽  
Author(s):  
Teresa R. De Kievit ◽  
Richard Gillis ◽  
Steve Marx ◽  
Chris Brown ◽  
Barbara H. Iglewski

ABSTRACT Acylated homoserine lactone molecules are used by a number of gram-negative bacteria to regulate cell density-dependent gene expression by a mechanism known as quorum sensing (QS). InPseudomonas aeruginosa, QS or cell-to-cell signaling controls expression of a number of virulence factors, as well as biofilm differentiation. In this study, we investigated the role played by the las and rhl QS systems during the early stages of static biofilm formation when cells are adhering to a surface and forming microcolonies. These studies revealed a marked difference in biofilm formation between the PAO1 parent and the QS mutants when glucose, but not citrate, was used as the sole carbon source. To further elucidate the contribution of lasI andrhlI to biofilm maturation, we utilized fusions to unstable green fluorescent protein in concert with confocal microscopy to perform real-time temporal and spatial studies of these genes in a flowing environment. During the course of 8-day biofilm development,lasI expression was found to progressively decrease over time. Conversely, rhlI expression remained steady throughout biofilm development but occurred in a lower percentage of cells. Spatial analysis revealed that lasI andrhlI were maximally expressed in cells located at the substratum and that expression decreased with increasing biofilm height. Because QS was shown previously to be involved in biofilm differentiation, these findings have important implications for the design of biofilm prevention and eradication strategies.


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