In vitro analysis of essential binding sites on the promoter of the <i>Serratia marcescens spn</i> operon with the quorum‐sensing receptor SpnR

Takayama, Yoichiro; Kato, Norihiro

doi:10.1002/bit.26013

Cited by 7 publications

(3 citation statements)

References 18 publications

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“…Moreover, the N-acylhomoserine lactone (AHL) receptor SpnR protein is a member in LuxR family that modulates S. marcescens QS. SpnR binds to S. marcescens DNA PLOS ONE on a lux-box like promoter to initiate a sequential QS process in the LuxR family [53]. In this context, it can be expected that the compounds which can regulate LuxI/LuxR system may have anti-QS activities, so then synthetic AHL analogues which inhibited Lux QS system were suggested as QS inhibitors [54].…”

Section: Discussionmentioning

confidence: 99%

Repurposing anti-diabetic drug “Sitagliptin” as a novel virulence attenuating agent in Serratia marcescens

Abbas

Hegazy

2020

PLoS ONE

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Background Serratia marcescens is an emerging pathogen that causes a variety of health care associated infections. S. marcescens is equipped with an arsenal of virulence factors such as biofilm formation, swimming and swarming motilities, prodigiosin, protease and others which enable it to initiate and cause the infection. These virulence factors are orchestrated under the umbrella of an intercellular communication system named Quorum sensing (QS). QS allows bacterial population to synchronize the expression of virulence genes upon detection of a chemical signaling molecule. Targeting bacterial virulence is a promising approach to attenuate bacteria and enhances the ability of immune system to eradicate the bacterial infection. Drug repurposing is an advantageous strategy that confers new applications for drugs outside the scope of their original medical use. This promising strategy offers the use of safe approved compounds, which potentially lowers the costs and shortens the time than that needed for development of new drugs. Sitagliptin is dipeptidyl peptidase-4 (DPP-4) inhibitor, is used to treat diabetes mellitus type II as it increases the production of insulin and decreasing the production of glucagon by the pancreas. We aimed in this study to repurpose sitagliptin, investigating the anti-virulence activities of sitagliptin on S. marcescens. Methods The effect of sub-inhibitory concentrations of sitagliptin on virulence factors; protease, prodigiosin, biofilm formation, swimming and swarming motilities was estimated phenotypically. The qRT-PCR was used to show the effect of sitagliptin on the expression of QS-regulated virulence genes. The in-vivo protective activity of sitagliptin on S. marcescens pathogenesis was evaluated on mice. Results Sitagliptin (1 mg/ml) significantly reduced the biofilm formation, swimming and swarming motilities, prodigiosin and protease. The qRT-PCR confirmed the effect on virulence as shown by down regulating the expression of fimA, fimC, flhC, flhD, bsmB, rssB, rsmA, pigP,

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Section: Discussionmentioning

confidence: 99%

Repurposing anti-diabetic drug “Sitagliptin” as a novel virulence attenuating agent in Serratia marcescens

Abbas

Hegazy

2020

PLoS ONE

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“…In the previous studies, we demonstrated the negative regulation of SpnR for the spn operon, which is related to the production of AHL-synthase and SpnR itself [8]. Specific interaction of SpnR with a promoter spn box was also proved in vitro by using a quartz crystal microbalance (QCM) analysis [9]. Fig.…”

Section: Introductionmentioning

confidence: 87%

Inhibition of Antimicrobial Prodigiosin Production in <i>Serratia marcescens</i> Using Cyclodextrin-Immobilized Microgel Beads Prepared by a Non-Contact Jet Dispensing System

Nasuno

Okano

Takayama

et al. 2017

AMM

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Some gram-negative bacteria possess N-acylhomoserine lactone (AHL)-mediated quorum sensing (QS) as one of the cell-to-cell communication systems for regulation of various cell functions. Increase in the AHL concentration above its threshold leads to simultaneous activation of target gene expression in each cell. The AHL can diffuse in and out of the cells through the cell membrane. Artificial reduction of the AHL concentration can inhibit the AHL complex formation with its receptor inside the cell. In this study, the AHL that diffused out into the culture broth was captured on α-cyclodextrin (CD), which possesses a hydrophobic cavity and a hydrophilic shell. The α-CD-immobilized calcium alginate gel beads, which were prepared using a non-contact jet dispenser, were immersed in the culture medium during the cell growth of Serratia marcescens AS-1, which was used as the model opportunistic human pathogen. The trapping of AHLs on immobilized α-CDs due to hydrophobic interaction of the AHL acyl-chain led to an effective inhibition of AHL-mediated prodigiosin production to approximately 2% in the presence of 27 wt% gel beads in the culture broth. The results of our study suggest that CD has high potential to regulate QS involved in matter production, biofilm formation, and virulence factor expression.

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“…The exchange of information between cells in an algae–bacteria system is conducted by quorum sensing, in which acyl-homoserine lactones (AHLs) are important signal molecules in the intercellular communication of gram-negative bacteria [ 19 ]. AHLs can affect bacteria activities, such as biofilm formation [ 20 , 21 , 22 ], pigment synthesis [ 23 ], and antibiotic synthesis [ 24 ]. Therefore, they play an important role in wastewater treatment technology [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of the N-hexanoyl-L-homoserine Lactone on the Carbon Fixation Capacity of the Algae–Bacteria System

Liao

Chen

Deng

et al. 2023

IJERPH

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Algae–bacteria systems are used widely in wastewater treatment. N-hexanoyl-L-homoserine lactone (AHL) plays an important role in algal-bacteria communication. However, little study has been conducted on the ability of AHLs to regulate algal metabolism and the carbon fixation ability, especially in algae–bacteria system. In this study, we used the Microcystis aeruginosa + Staphylococcus ureilyticus strain as a algae–bacteria system. The results showed that 10 ng/L C6-HSL effectively increased the chlorophyll-a (Chl-a) concentration and carbon fixation enzyme activities in the algae–bacteria group and algae group, in which Chl-a, carbonic anhydrase activity, and Rubisco enzyme increased by 40% and 21%, 56.4% and 137.65%, and 66.6% and 10.2%, respectively, in the algae–bacteria group and algae group, respectively. The carbon dioxide concentration mechanism (CCM) model showed that C6-HSL increased the carbon fixation rate of the algae–bacteria group by increasing the CO2 transport rate in the water and the intracellular CO2 concentration. Furthermore, the addition of C6-HSL promoted the synthesis and secretion of the organic matter of algae, which provided biogenic substances for bacteria in the system. This influenced the metabolic pathways and products of bacteria and finally fed back to the algae. This study provided a strategy to enhance the carbon fixation rate of algae–bacteria consortium based on quorum sensing.

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In vitro analysis of essential binding sites on the promoter of the Serratia marcescens spn operon with the quorum‐sensing receptor SpnR

Cited by 7 publications

References 18 publications

Repurposing anti-diabetic drug “Sitagliptin” as a novel virulence attenuating agent in Serratia marcescens

Repurposing anti-diabetic drug “Sitagliptin” as a novel virulence attenuating agent in Serratia marcescens

Inhibition of Antimicrobial Prodigiosin Production in <i>Serratia marcescens</i> Using Cyclodextrin-Immobilized Microgel Beads Prepared by a Non-Contact Jet Dispensing System

Effect of the N-hexanoyl-L-homoserine Lactone on the Carbon Fixation Capacity of the Algae–Bacteria System

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