La Sr Research Articles

The Role of SprIR Quorum Sensing System in the Regulation of Serratia proteamaculans 94 Invasion.

The bacteria Serratia proteamaculans 94 have a LuxI/LuxR type QS system consisting of AHL synthase SprI and the regulatory receptor SprR. We have previously shown that inactivation of the AHL synthase sprI gene resulted in an increase in the invasive activity of S. proteamaculans correlated with an increased bacterial adhesion. In the present work, the effects of inactivation of the S. proteamaculans receptor SprR are studied. Our results show that inactivation of the receptor sprR gene leads to an increase in bacterial invasion without any increase in their adhesion. On the other hand, inactivation of the sprR gene increases the activity of the extracellular protease serralysin. Inactivation of the QS system does not affect the activity of the pore-forming toxin ShlA and prevents the ShlA activation under conditions of a limited concentration of iron ions typical of the human body. While the wild type strain shows increased invasion in the iron-depleted medium, deletion of its QS system leads to a decrease in host cell invasion, which is nevertheless similar to the level of the wild type S. proteamaculans grown in the iron-rich medium. Thus, inactivation of either of the two component of the S. proteamaculans LuxI/LuxR-type QS system leads to an increase in the invasive activity of these bacteria through different mechanisms and prevents invasion under the iron-limited conditions.

LitR directly upregulates autoinducer synthesis and luminescence in Aliivibrio logei.

LitR is a master-regulator of transcription in the ainS/R and luxS/PQ quorum sensing (QS) systems of bacteria from Vibrio and Aliivibrio genera. Here, we for the first time directly investigated the influence of LitR on gene expression in the luxI/R QS system of psychrophilic bacteria Aliivibrio logei. Investigated promoters were fused with Photorhabdus luminescens luxCDABE reporter genes cassette in a heterological system of Escherichia coli cells, litR A. logei was introduced into the cells under control of Plac promoter. LitR has been shown to upregulate genes of autoinducer synthase (luxI), luciferase and reductase (luxCDABE), and this effect doesn’t depend on presence of luxR gene. To a much lesser degree, LitR induces luxR1, but not the luxR2 — the main luxI/R regulator. Enhanced litR expression leads to an increase in a LuxI-autoinducer synthesis and a subsequent LuxR-mediated activation of the luxI/R QS system. Effect of LitR on luxI transcription depends on lux-box sequence in luxI promoter even in absence of luxR (lux-box is binding site of LuxR). The last finding indicates a direct interaction of LitR with the promoter in the lux-box region. Investigation of the effect of LitR A. logei on luxI/R QS systems of mesophilic Aliivibrio fischeri and psychrophilic Aliivibrio salmonicida showed direct luxR-independent upregulation of luxI and luxCDABE genes. To a lesser degree, it induces luxR A. fischeri and luxR1 A. salmonicida. Therefore, we assume that the main role of LitR in cross-interaction of these three QS systems is stimulating the expression of luxI.

Quorum sensing-1 signaling of N-hexanoyl-L-homoserine lactone contributes to virulence in avian pathogenic Escherichia coli.

Avian pathogenic E. coli (APEC) caused avian colibacillosis is mostly common in poultry industry worldwide. APEC virulence factors lead to pathogenesis and the quorum sensing (QS) system is actively involved in the regulation of these virulence factors. Signaling molecules in QS are known as autoinducers (AIs). In QS-1, E. coli encodes a single LuxR homolog, i.e., SdiA, but does not express the LuxI homolog, an acyl-homoserine lactone (AHL) synthase of producing AI-1. Avian pathogenic E. coli (APEC) regulates its virulence genes expression in response to exogenous AHLs, but regulatory mechanisms of AHL and QS-1 are still unknown. This study targeted the APEC CE129 isolate as the reference strain, and the Yersinia enterocolitica yenI gene was expressed into APEC CE129. CE129/pyenI was conferred the ability to produce AHL signal. The CE129 SdiA mutant strain with an in-frame sdiA (AHL receptor) gene deletion was constructed by a λRed recombination system, which lost the ability to sense AHL. The goal of this study was to explore the function of QS-1 upon virulence and elucidate the regulatory effect of QS-1/AHL signals in the APEC strain. Adherence and invasion assays revealed that QS-1 affected APEC adherence and survival ability. APEC biofilm formation was also suppressed under C6HSL. Interestingly, APEC exhibited different phenotypes of acid tolerance and flagella expression when compared to enterotoxigenic E. coli or enterohemorrhagic E. coli (ETEC and EHEC, respectively). These findings enhance our understanding of the QS mechanism.

Ингибирование бактериального кворум сенсинга (общие представления)

В научном обзоре изложены современные данные, характеризующие основные положения о функционировании механизма кворум сенсинга в системе межбактериальных коммуникаций. Представлена общая характеристика различных соединений, обладающих подавляющим влиянием на кворум сенсинг. Подчеркнуто, что по механизму ингибиторы кворум сенсинга представляют три функциональные группы: 1) группа веществ, подавляющих активность аутоиндукторных синтаз; 2) группа веществ, блокирующих аутоиндукторные рецепторы; 3) группа веществ, нарушающих взаимодействие аутоиндукторов с их специфическим рецептором.

Assessment of Antibiofilm Potencies of Nervonic and Oleic Acid against Acinetobacter baumannii Using In Vitro and Computational Approaches.

Acinetobacter baumannii is a nosocomial pathogen, and its biofilms are tolerant to desiccation, nutrient starvation, and antimicrobial treatment on biotic and abiotic surfaces, tissues, and medical devices. Biofilm formation by A. baumannii is triggered by a quorum sensing cascade, and we hypothesized that fatty acids might inhibit its biofilm formation by interfering with quorum sensing. Initially, we investigated the antibiofilm activities of 24 fatty acids against A. baumannii ATCC 17978 and two clinical isolates. Among these fatty acids, two unsaturated fatty acids, nervonic and oleic acid, at 20 μg/mL significantly inhibited A. baumannii biofilm formation without affecting its planktonic cell growth (MICs were >500 μg/mL) and markedly decreased the motility of A. baumannii but had no toxic effect on the nematode Caenorhabditis elegans. Interestingly, molecular dynamic simulations showed that both fatty acids bind to the quorum sensing acyl homoserine lactone synthase (AbaI), and decent conformational stabilities of interactions between the fatty acids and AbaI were exhibited. Our results demonstrate that nervonic and oleic acid inhibit biofilm formation by A. baumannii strains and may be used as lead molecules for the control of persistent A. baumannii infections.

Hfq and sRNA00002 positively regulate the LuxI/LuxR-type quorum sensing system in Pseudoalteromonas

Pseudoalteromonas spp. are Gram-negative bacteria which are ubiquitous in marine environments. Our previous work found that there is a classic LuxI/LuxR-type quorum sensing (QS) system which was named YasI/YasR in Pseudoalteromonas sp. R3, but the factors that control QS in strain R3 are unclear yet. Here, we found that the deficiency of hfq encoding RNA chaperon Hfq down-regulated the transcription levels of yasI encoding acyl-homoserine lactones (AHLs) synthase and yasR encoding AHLs receptor in strain R3. The assay based on fusion reporter of yasI-lacZ showed that Hfq regulates the expression of yasR at both transcriptional and translational levels. In addition, Hfq affects the expression of yasI via yasR. Further analysis indicated that the 5′UTR region of yasR is necessary for Hfq to control QS. In addition, the deletion of hfq increases the unstability of the target yasR mRNA. Based on transcriptome sequencing and bioinformatic analysis together with molecular experiments, Hfq-dependent sRNA00002 was identified to be involved in positively regulating QS in Pseudoalternas sp. R3. It was found that sRNA00002 deficiency causes the decrease in expression of yasI and yasR, and thus abolishes the production of AHLs in strain R3. It was concluded that Hfq-dependent sRNA00002 regulates yasR expression by base-pairing with target yasR mRNA at 5′UTR region and altering the stability of yasR mRNA. Our work paves the way for understanding the regulation mechanism of Hfq-dependent sRNAs on QS in Pseudoalteromonas.

Coumarin Exhibits Broad-Spectrum Antibiofilm and Antiquorum Sensing Activity against Gram-Negative Bacteria: In Vitro and In Silico Investigation.

Quorum sensing (QS) and biofilm inhibition are recognized as the novel drug targets for the broad-spectrum anti-infective strategy to combat the infections caused by drug-resistant bacterial pathogens. Many compounds from medicinal plants have been found to demonstrate anti-infective activity. However, broad-spectrum anti-QS and antibiofilm efficacy and their mode of action are poorly studied. In this study, the efficacy of coumarin was tested against QS-regulated virulent traits of Gram-negative bacteria. Coumarin inhibited the production of violacein pigment in Chromobacterium violaceum 12472 by 64.21%. Similarly, there was 87.25, 70.05, 76.07, 58.64, 48.94, and 81.20% inhibition of pyocyanin, pyoverdin, and proteolytic activity, lasB elastase activity, swimming motility, and rhamnolipid production, respectively, in Pseudomonas aeruginosa PAO1. All tested virulence factors of Serratia marcescens MTCC 97 were also suppressed by more than 50% at the highest sub-minimum inhibitory concentration. Moreover, the biofilms of bacterial pathogens were also inhibited in a dose-dependent manner. Molecular docking and molecular dynamics (MD) simulation gave insights into the possible mode of action. The binding energy obtained by docking studies ranged from −5.7 to −8.1 kcal mol–1. Coumarin was found to be docked in the active site of acylhomoserine lactone (AHL) synthases and regulatory proteins of QS. MD simulations further supported the in vitro studies where coumarin formed a stable complex with the tested proteins. The secondary structure of all proteins showed a negligible change in the presence of coumarin. Computational studies showed that the possible mechanisms of anti-QS activity were the inhibition of AHL synthesis, antagonization of QS-regulatory proteins, and blocking of the receptor proteins. The findings of this study clearly highlight the potency of coumarin against the virulence factors of Gram-negative bacterial pathogens that may be developed as an effective inhibitor of QS and biofilms.

The abaI/abaR Quorum Sensing System Effects on Pathogenicity in Acinetobacter baumannii.

Acinetobacter baumannii is a Gram-negative pathogen that has emerged as one of the most troublesome pathogens for healthcare institutions globally. Bacterial quorum sensing (QS) is a process of cell-to-cell communication that relies on the production, secretion, and detection of autoinducer (AI) signals to share information about cell density and regulate gene expression accordingly. The molecular and genetic bases of A. baumannii virulence remains poorly understood. Therefore, the contribution of the abaI/abaR QS system to growth characteristics, morphology, biofilm formation, resistance, motility, and virulence of A. baumannii was studied in detail. RNA sequencing (RNA-seq) analysis indicated that genes involved in various aspects of energy production and conversion; valine, leucine, and isoleucine degradation; and lipid transport and metabolism are associated with bacterial pathogenicity. Our work provides a new insight into the abaI/abaR QS system effects on pathogenicity in A. baumannii. We propose that targeting the acyl homoserine lactone (AHL) synthase enzyme abaI could provide an effective strategy for attenuating virulence. On the contrary, interdicting the AI synthase receptor abaR elicits unpredictable consequences, which may lead to enhanced bacterial virulence.

Protein Model and Function Analysis in Quorum-Sensing Pathway of Vibrio qinghaiensis sp.-Q67.

Simple SummaryVibrio qinghaiensis sp.-Q67 (Q67) is a nonpathogenic freshwater luminescent bacterium and has been a focus due to its wide use in the monitoring of environmental pollution and the assessment of toxicity, using the luminescence inhibition rate as the end point. However, the lack of available crystal structures limits the elucidation of the structures of the functional proteins of the quorum-sensing (QS) system that regulates bacterial luminescence in Q67. In this study, homologous models of 19 proteins potentially involved in QS and bioluminescence in Q67 were built using MODELLER. Then, we analyzed the predicted structures and functions of these proteins one by one by combining the existing proteins to explore how the QS pathway of Q67 regulated bioluminescence at the molecular level. This study not only provides a database of predicted protein molecular structures for exploring the mechanisms of the toxicity of chemicals from a molecular point of view, but also indirectly summarizes the research status of crystal structure and function analysis in QS systems, providing references and guidance for follow-up research.Bioluminescent bacteria are mainly found in marine habitats. Vibrio qinghaiensis sp.-Q67 (Q67), a nonpathogenic freshwater bacterium, has been a focus due to its wide use in the monitoring of environmental pollution and the assessment of toxicity. However, the lack of available crystal structures limits the elucidation of the structures of the functional proteins of the quorum-sensing (QS) system that regulates bacterial luminescence in Q67. In this study, 19 functional proteins were built through monomer and oligomer modeling based on their coding proteins in the QS system of Q67 using MODELLER. Except for the failure to construct LuxM due to the lack of a suitable template, 18 functional proteins were successfully constructed. Furthermore, the relationships between the function and predicted structures of 19 functional proteins were explored one by one according to the three functional classifications: autoinducer synthases and receptors, signal transmission proteins (phosphotransferases, an RNA chaperone, and a transcriptional regulator), and enzymes involved in bacterial bioluminescence reactions. This is the first analysis of the whole process of bioluminescence regulation from the perspective of nonpathogenic freshwater bacteria at the molecular level. It provides a theoretical basis for the explanation of applications of Q67 in which luminescent inhibition is used as the endpoint.

Invasion of Serratia proteamaculans is regulated by the sprI gene encoding AHL synthase

Quorum Sensing (QS) system regulates gene expression in response to a change in the density of the bacterial population. Facultative pathogen Serratia proteamaculans 94 has a LuxI/LuxR type QS system consisting of regulatory protein SprR and AHL synthase SprI. Invasive activity of these bacteria appears at the stationary growth phase corresponding to a maximal density of the bacterial population in vitro. To evaluate the contribution of QS system of S. proteamaculans 94 to the regulation of invasive activity, in this work, S. proteamaculans SprI(−) mutant carrying the inactivated AHL synthase gene was used. Inactivation of the AHL synthase sprI gene resulted in a more than fourfold increase in the invasive activity of S. proteamaculans preceded by the increased adhesion of bacteria to the cell surface. This effect correlated with the increased expression of the outer membrane protein ompX gene and the decrease in the activity of intrabacterial protease protealysin, whose substrate is OmpX. The inverse correlation between activity of protealysin and bacterial invasion was also observed in the model experiments under the iron-limiting culture conditions. These results show that QS system regulates the S. proteamaculans invasion. This regulation can involve changes both in the protealysin activity and in the level of the ompX gene transcription.

Blue light directly modulates the quorum network in the human pathogen Acinetobacter baumannii

Quorum sensing modulates bacterial collective behaviors including biofilm formation, motility and virulence in the important human pathogen Acinetobacter baumannii. Disruption of quorum sensing has emerged as a promising strategy with important therapeutic potential. In this work, we show that light modulates the production of acyl-homoserine lactones (AHLs), which were produced in higher levels in the dark than under blue light at environmental temperatures, a response that depends on the AHL synthase, AbaI, and on the photoreceptor BlsA. BlsA interacts with the transcriptional regulator AbaR in the dark at environmental temperatures, inducing abaI expression. Under blue light, BlsA does not interact with AbaR, but induces expression of the lactonase aidA and quorum quenching, consistently with lack of motility at this condition. At temperatures found in warm-blooded hosts, the production of AHLs, quorum quenching as well as abaI and aidA expression were also modulated by light, though in this case higher levels of AHLs were detected under blue light than in the dark, in a BlsA-independent manner. Finally, AbaI reduces A. baumannii's ability to kill C. albicans only in the dark both at environmental as well as at temperatures found in warm-blooded hosts. The overall data indicate that light directly modulates quorum network in A. baumannii.

A covariation analysis reveals elements of selectivity in quorum sensing systems.

Many bacteria communicate with kin and coordinate group behaviors through a form of cell-cell signaling called acyl-homoserine lactone (AHL) quorum sensing (QS). In these systems, a signal synthase produces an AHL to which its paired receptor selectively responds. Selectivity is fundamental to cell signaling. Despite its importance, it has been challenging to determine how this selectivity is achieved and how AHL QS systems evolve and diversify. We hypothesized that we could use covariation within the protein sequences of AHL synthases and receptors to identify selectivity residues. We began by identifying about 6000 unique synthase-receptor pairs. We then used the protein sequences of these pairs to identify covariation patterns and mapped the patterns onto the LasI/R system from Pseudomonas aeruginosa PAO1. The covarying residues in both proteins cluster around the ligand-binding sites. We demonstrate that these residues are involved in system selectivity toward the cognate signal and go on to engineer the Las system to both produce and respond to an alternate AHL signal. We have thus demonstrated that covariation methods provide a powerful approach for investigating selectivity in protein-small molecule interactions and have deepened our understanding of how communication systems evolve and diversify.

Quorum sensing inhibitory effect of bergamot oil and aspidosperma extract against Chromobacterium violaceum and Pseudomonas aeruginosa.

Quorum sensing (QS) represents a major target for reducing bacterial pathogenicity and antibiotic resistance. This study identifies bergamot and aspidosperma as new potential sources of anti-QS agents. We investigated the anti-QS activity of plant materials on both Chromobacterium violaceum and Pseudomonas aeruginosa. Initially, we determined the minimum inhibitory concentrations (MICs) of plant materials using a broth microdilution method. Subsequently, we tested the effect of sub-MIC concentrations on QS-regulated traits and virulence factors production in test bacteria. Results revealed that bergamot and aspidosperma inhibited the ability of C. violaceum to produce violacein. Other QS-controlled phenotypes of C. violaceum, namely chitinolytic activity, motility, and biofilm formation, were also reduced by both plant materials. Moreover, QS-linked traits of P. aeruginosa were also reduced. Bergamot inhibited swarming but not swimming motility, while aspidosperma diminished both motility types in P. aeruginosa. Both plant materials also demonstrated antibiofilm activity and inhibited the production of protease and pyocyanin in P. aeruginosa. Furthermore, we tested the anti-QS effect of plant materials on the transcriptional level using RT-qPCR. Bergamot dramatically downregulated the C. violaceum autoinducer synthase gene cviI and the vioB gene involved in violacein biosynthesis, confirming the phenotypic observation on its anti-QS activity. Aspidosperma also reduced the expression of cviI and vioB but less drastically than bergamot. In P. aeruginosa, downregulation in the transcripts of the QS genes lasI, lasR, rhlI, and rhlR was also achieved by bergamot and aspidosperma. Therefore, data in the present study suggest the usefulness of bergamot and aspidosperma as sources of antivirulence agents.

Phloretin, an Apple Phytoalexin, Affects the Virulence and Fitness of Pectobacterium brasiliense by Interfering With Quorum-Sensing

The effects of phloretin a phytoalexin from apple, was tested on Pectobacterium brasiliense (Pb1692), an emerging soft-rot pathogen of potato. Exposure of Pb1692 to 0.2 mM phloretin a concentration that does not affect growth, or to 0.4 mM a 50% growth inhibiting concentration (50% MIC), reduced motility, biofilm formation, secretion of plant cell wall-degrading enzymes, production of acyl–homoserine lactone (AHL) signaling molecules and infection, phenotypes that are associated with bacterial population density-dependent system known as quorum sensing (QS). To analyze the effect of growth inhibition on QS, the activity of ciprofloxacin, an antibiotic that impairs cell division, was compared to that of phloretin at 50% MIC. Unlike phloretin, the antibiotic hardly affected the tested phenotypes. The use of DH5α, a QS-negative Escherichia coli strain, transformed with an AHL synthase (ExpI) from Pb1692, allowed to validate direct inhibition of AHL production by phloretin, as demonstrated by two biosensor strains, Chromobacterium violaceaum (CV026) and E. coli (pSB401). Expression analysis of virulence-related genes revealed downregulation of QS-regulated genes (expI, expR, luxS, rsmB), plant cell wall degrading enzymes genes (pel, peh and prt) and motility genes (motA, fim, fliA, flhC and flhD) following exposure to both phloretin concentrations. The results support the inhibition of ExpI activity by phloretin. Docking simulations were used to predict the molecular associations between phloretin and the active site of ExpI, to suggest a likely mode of action for the compound’s inhibition of virulence.

Structural insights into acyl-ACP selective recognition by the Aeromonas hydrophila AHL synthase AhyI

BackgroundAeromonas hydrophila is a gram-negative bacterium and the major causative agent of the fish disease motile aeromonad septicemia (MAS). It uses N-acyl-homoserine lactone (AHL) quorum sensing signals to coordinate biofilm formation, motility, and virulence gene expression. The AHL signaling pathway is therefore considered to be a therapeutic target against pathogenic A. hydrophila infection. In A. hydrophila, AHL autoinducers biosynthesis are specifically catalyzed by an ACP-dependent AHL synthase AhyI using the precursors SAM and acyl-ACP. Our previously reported AhyI was heterologously expressed in E. coli, which showed the production characteristics of medium-long chain AHLs. This contradicted the prevailing understanding that AhyI was only a short-chain C4/C6-HSL synthase.ResultsIn this study, six linear acyl-ACP proteins with C-terminal his-tags were synthesized in Vibrio harveyi AasS using fatty acids and E. coli produced active holo-ACP proteins, and in vitro biosynthetic assays of six AHL molecules and kinetic studies of recombinant AhyI with a panel of four linear acyl-ACPs were performed. UPLC-MS/MS analyses indicated that AhyI can synthesize short-, medium- and long-chain AHLs from SAM and corresponding linear acyl-ACP substrates. Kinetic parameters measured using a DCPIP colorimetric assay, showed that there was a notable decrease in catalytic efficiency with acyl-chain lengths above C6, and hyperbolic or sigmoidal responses in rate curves were observed for varying acyl-donor substrates. Primary sequence alignment of the six representative AHL synthases offers insights into the structural basis for their specific acyl substrate preference. To further understand the acyl chain length preference of AhyI for linear acyl-ACP, we performed a structural comparison of three ACP-dependent LuxI homologs (TofI, BmaI1 and AhyI) and identified three key hydrophobic residues (I67, F125 and L157) which confer AhyI to selectively recognize native C4/C6-ACP substrates. These predictions were further supported by a computational Ala mutation assay.ConclusionsIn this study, we have redefined AhyI as a multiple short- to long-chain AHL synthase which uses C4/C6-ACP as native acyl substrates and longer acyl-ACPs (C8 ~ C14) as non-native ones. We also theorized that the key residues in AhyI would likely drive acyl-ACP selective recognition.

Enhancing Electrochemical CO2 Reduction using Ce(Mn,Fe)O2 with La(Sr)Cr(Mn)O3 Cathode for High‐Temperature Solid Oxide Electrolysis Cells

AbstractRobust oxide electrodes with high activity and durability have attracted significant attention as alternatives for Ni‐based cathodes in high‐temperature solid oxide electrolysis cells (SOECs). Noncoking La(Sr)Cr(Mn)O3 (LSCM)‐based oxide cathodes have shown promise as durable ceramic cathodes; however, they suffer from low electrocatalytic activities in electrochemical CO2 reduction. In this study, a dual‐phase composite electrode consisting of LSCM and Ce(Mn, Fe)O2 (CMF) is developed to enhance the electrocatalytic activity of CO2 reduction in SOECs. The developed electrode shows excellent electrolysis performance of 2.64 and 1.22 A cm–2 at 1123 K, when voltages of 1.5 and 1.2 V are applied, respectively, without using any precious metal catalysts. The enhanced electrolysis performance is attributed to increases in electrocatalytic activity and surface oxygen vacancies caused by the CMF, which accelerates CO2 adsorption and results in the subsequent dissociation of the carbonate intermediate in the CO2 reduction.

Formation of a Dense La(Sr)Fe(Ga)O3 Interlayer at the Electrolyte/Porous Cathode Interface by Magnetron Sputtering and Its Effect on the Cathode Characteristics

Formation of a Dense La(Sr)Fe(Ga)O3 Interlayer at the Electrolyte/Porous Cathode Interface by Magnetron Sputtering and Its Effect on the Cathode Characteristics

Anti-quorum sensing and antibiofilm potential of 1,8-cineole derived from Musa paradisiaca against Pseudomonas aeruginosa strain PAO1.

Pseudomonas aeruginosa is one of the vulnerable opportunistic pathogens associated with nosocomial infections, cystic fibrosis, burn wounds and surgical site infections. Several studies have reported that quorum sensing (QS) systems are controlled the P. aeruginosa pathogenicity. Hence, the targeting of QS considered as an alternative approach to control P. aeruginosa infections. This study aimed to evaluate the anti-quorum sensing and antibiofilm inhibitory potential of Musa paradisiaca against Chromobacterium violaceum (ATCC 12472) and Pseudomonas aeruginosa. The methanol extract of M. paradisiacsa exhibits that better antibiofilm potential against P. aeruginosa. Then, the crude methanol extract was subjected to purify by column chromatography and collected the fractions. The mass-spectrometric analysis of a methanol extract of M. paradisiaca revealed that 1,8-cineole is the major compounds. 1, 8-cineole significantly inhibited the QS regulated violacein production in C. violaceum. Moreover, 1,8-cineole significantly inhibited the QS mediated virulence production and biofilm formation of P. aeruginosa without affecting their growth. The real-time PCR analysis showed the downregulation of autoinducer synthase and transcriptional regulator genes upon 1,8-cineole treatment. The findings of the present study strongly suggested that metabolite of M. paradisiaca impedes P. aeruginosa QS system and associated virulence productions.

The difference of PMMA‐brush‐modification on the oxygen permeable perovskite‐type oxides by consisting elements

AbstractOxygen permeation of perovskite‐type ceramics consists of three elementary processes: oxygen absorption, bulk oxygen diffusion, and oxygen desorption. In most cases, the rate‐determining step is the oxygen diffusion step, and the use of thin films improves the oxygen permeation rate of perovskite‐type ceramics. Polymer‐brush‐modification is a useful technique to produce thin films. Grafted PMMA‐brushes exhibit a screening effect for attractive interactions between core ceramic particles, thereby inducing repulsive forces on them. This results in the formation of a densely packed ordered array. Modification of the polymerization‐initiator and polymer‐brushes should affect the oxygen permeation properties of the ceramic particles, especially surface oxygen adsorption and desorption. In this paper, it is demonstrated that these modifications change the cation chemical states and lower the oxygen desorption rate, while increasing the desorption peak temperature. The surface of La–Sr–Co–Fe perovskite‐type oxides was modified only with the polymerization initiator, (2‐bromo‐2‐methyl)propionyloxyhexyltriethoxysilane (BHE) because there is no direct interaction between the polymer‐brush and the substrate, while the initiator is directly modified to the substrate. The oxygen desorption behavior of BHE‐modified oxides indicates that its oxygen desorption property is impeded without modification with PMMA. The investigation of BHE‐modified oxide cation chemical states and oxygen desorption behaviors imply that the BHE‐modifying site and change in chemical states have selectivity depending on cation species. Although sintering causes the formation of silicate and ceramic decomposition, this step can eliminate the harmful effects of BHE‐modification in total. When conventional La–Sr–Co–Fe perovskite‐type ceramics are used, sintering is preferable for the recovery of thin‐film surface reactions. However, if we utilize site selectivity of BHE‐modification, the harmful effects of those modifications can be avoided by modifying BHE onto sites that hardly participate in surface reactions.

Design, synthesis, and evaluation of transition-state analogs as inhibitors of the bacterial quorum sensing autoinducer synthase CepI

Quorum sensing is a bacterial signaling system that involves the synthesis, secretion and detection of signal molecules called autoinducers. The main autoinducer in Gram-negative bacteria are acylated homoserine lactones, produced by the LuxI family of autoinducer synthases and detected by the LuxR family of autoinducer receptors. Quorum sensing allows for changes in gene expression and bacterial behaviors in a coordinated, cell density dependent manner. Quorum sensing controls the expression of virulence factors in some human pathogens, making quorum sensing an antibacterial drug target. Here we describe the design and synthesis of transition-state analogs of the autoinducer synthase enzymatic reaction and the evaluation of these compounds as inhibitors of the synthase CepI. One such compound potently inhibits CepI and constitutes a new type of inhibitor against this underdeveloped antibacterial target.