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https://www.readbyqxmd.com/read/28096154/influence-of-rhlr-and-lasr-on-polymyxin-pharmacodynamics-in-pseudomonas-aeruginosa-implications-for-quorum-sensing-inhibition-with-azithromycin
#1
Zackery P Bulman, Neang S Ly, Justin R Lenhard, Patricia N Holden, Jürgen B Bulitta, Brian T Tsuji
Quorum sensing's impact on polymyxin and azithromycin pharmacodynamics was assessed in Pseudomonas aeruginosa PAO1 and an isogenic rhlR/lasR double knockout. For polymyxin B, greater killing against the rhlR/lasR knockout versus PAO1 was observed at 10(8) CFU/mL(polymyxin B EC50:5.61 versus 12.5mg/L, respectively; p<0.005). Polymyxin B combined with azithromycin (256mg/L) was synergistic against each strain, significantly reducing the respective polymyxin B EC50 compared to monotherapy (p<0.005), and is a promising strategy to combat P...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28075113/pseudomonas-aeruginosa-lasr%C3%A2-dna-binding-is-directly-inhibited-by-quorum-sensing-antagonists
#2
Emma G Suneby, Leslie R Herndon, Tanya L Schneider
Inhibition of quorum sensing in Pseudomonas aeruginosa is of interest as a possible antivirulence strategy for this pathogenic bacterium. The LasR regulator protein is important in coordinating gene expression in response to quorum sensing signaling molecules. One predominant strategy for LasR inhibition is the development of small-molecule antagonists that mimic the native autoinducer, though the mechanism by which they inactivate LasR is not known. This work reveals that multiple antagonists function by binding to and stabilizing LasR in a conformation that renders it unable to bind DNA...
January 11, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28065820/bioavailability-enhanced-resveramax%C3%A2-modulates-quorum-sensing-and-inhibits-biofilm-formation-in-pseudomonas-aeruginosa-pao1
#3
H S Vasavi, H V Sudeep, H B Lingaraju, K Shyam Prasad
Quorum sensing (QS), a cell-to-cell communication mechanism present in many bacterial species plays a key role in regulating the virulence factor and biofilm formation in many pathogens, which causes severe public health risk. Therefore, interfering with QS mechanism offers an attractive strategy to combat bacterial infections. In the present study, anti-QS activity of a novel resveratrol formulation, Resveramax™, was detected using Chromobacterium violaceum biosensor bioassay and the effect of Resveramax on QS-regulated phenotypes in Pseudomonas aeruginosa PAO1 was assessed by standard protocols...
January 5, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28064429/structural-insight-into-the-gene-expression-profiling-of-the-hcn-operon-in-pseudomonas-aeruginosa
#4
Nilkanta Chowdhury, Angshuman Bagchi
Pseudomonas aeruginosa is a common opportunistic human pathogen. It generally attacks immunosuppressed patients like AIDS, cancer, cystic fibrosis, etc. The virulence of P. aeruginosa is mediated by various virulence factors. One of such potential virulence factors is HCN synthesized by HCN synthase enzyme, which is encoded by the hcnABC operon. The expressions of the genes of this operon are regulated by three transcriptional regulators, viz., LasR, ANR, and RhlR. In our previous work, we analyzed the molecular details of the functionalities of LasR...
January 7, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28049617/synthesis-of-antimicrobial-glucosamides-as-bacterial-quorum-sensing-mechanism-inhibitors
#5
Nripendra N Biswas, Tsz Tin Yu, Önder Kimyon, Shashidhar Nizalapur, Christopher R Gardner, Mike Manefield, Renate Griffith, David StC Black, Naresh Kumar
Bacteria communicate with one another and regulate their pathogenicity through a phenomenon known as quorum sensing (QS). When the bacterial colony reaches a threshold density, the QS system induces the production of virulence factors and the formation of biofilms, a powerful defence system against the host's immune responses. The glucosamine monomer has been shown to disrupt the bacterial QS system by inhibiting autoinducer (AI) signalling molecules such as the acyl-homoserine lactones (AHLs). In this study, the synthesis of acetoxy-glucosamides 8, hydroxy-glucosamides 9 and 3-oxo-glucosamides 12 was performed via the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) and N,N'-dicyclohexylcarbodiimide (DCC) coupling methods...
December 21, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28010047/distal-and-proximal-promoters-co-regulate-pqsr-expression-in-pseudomonas-aeruginosa
#6
John M Farrow, Everett C Pesci
The ubiquitous bacterium Pseudomonas aeruginosa is an opportunistic pathogen that can cause serious infections in immunocompromised individuals. P. aeruginosa virulence is controlled partly by intercellular communication, and the transcription factor PqsR is a necessary component in the P. aeruginosa cell-to-cell signaling network. PqsR acts as the receptor for the Pseudomonas quinolone signal, and it controls the production of 2-alkyl-4-quinolone molecules which are important for pathogenicity. Previous studies showed that the expression of pqsR is positively controlled by the quorum-sensing regulator LasR, but it was unclear how LasR is able to induce pqsR transcription...
December 23, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/28000767/a-diketopiperazine-factor-from-rheinheimera-aquimaris-qsi02-exhibits-anti-quorum-sensing-activity
#7
Shiwei Sun, Xiaoyun Dai, Jiao Sun, Xiangguo Bu, Caihong Weng, Hui Li, Hu Zhu
An ethyl acetate (EtOAc) extract isolated from the marine bacterium, Rheinheimera aquimaris QSI02, was found to exhibit anti-quorum sensing (anti-QS) activity. A subsequent bioassay-guided isolation protocol led to the detection of an active diketopiperazine factor, cyclo(Trp-Ser). Biosensor assay data showed that the minimum inhibitory concentration (MIC) of cyclo(Trp-Ser) ranged from 3.2 mg/ml to 6.4 mg/m for several microorganisms, including Escherichia coli, Chromobacterium violaceum CV026, Pseudomonas aeruginosa PA01, Staphylococcus aureus, and Candida albicans...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924027/crystal-structure-of-pseudomonas-aeruginosa-rsal-bound-to-promoter-dna-reaffirms-its-role-as-a-global-regulator-involved-in-quorum-sensing
#8
Huaping Kang, Jianhua Gan, Jingru Zhao, Weina Kong, Jing Zhang, Miao Zhu, Fan Li, Yaqin Song, Jin Qin, Haihua Liang
Pseudomonas aeruginosa possesses at least three well-defined quorum-sensing (QS) (las, rhl and pqs) systems that control a variety of important functions including virulence. RsaL is a QS repressor that reduces QS signal production and ensures homeostasis by functioning in opposition to LasR. However, its regulatory role in signal homeostasis remains elusive. Here, we conducted a ChIP-seq assay and revealed that RsaL bound to two new targets, the intergenic regions of PA2228/PA2229 and pqsH/cdpR, which are required for PQS synthesis...
October 18, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27902425/virulence-adaptations-of-pseudomonas-aeruginosa-isolated-from-patients-with-non-cystic-fibrosis-bronchiectasis
#9
Taylor Evart Woo, Jessica Duong, Nicole M Jervis, Harvey R Rabin, Michael D Parkins, Douglas Gordon Storey
Pseudomonas aeruginosa is a major pathogen in chronic lung diseases such as cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis (nCFB). Much of our understanding regarding infections in nCFB patients is extrapolated from findings in CF with little direct investigation on the adaptation of P. aeruginosa in nCFB patients. As such, we investigated whether the adaptation of P. aeruginosa was indeed similar between nCFB and CF. From our prospectively collected biobank we identified 40 nCFB patients who had repeated P...
November 8, 2016: Microbiology
https://www.readbyqxmd.com/read/27900439/non-ribosomal-peptide-synthases-from-pseudomonas-aeruginosa-play-a-role-in-cyclodipeptide-biosynthesis-quorum-sensing-regulation-and-root-development-in-a-plant-host
#10
Omar González, Randy Ortíz-Castro, César Díaz-Pérez, Alma L Díaz-Pérez, Viridiana Magaña-Dueñas, José López-Bucio, Jesús Campos-García
Diverse molecules mediate cross-kingdom communication between bacteria and their eukaryotic partners and determine pathogenic or symbiotic relationships. N-acyl-L-homoserine lactone-dependent quorum-sensing signaling represses the biosynthesis of bacterial cyclodipeptides (CDPs) that act as auxin signal mimics in the host plant Arabidopsis thaliana. In this work, we performed bioinformatics, biochemical, and plant growth analyses to identify non-ribosomal peptide synthase (NRPS) proteins of Pseudomonas aeruginosa, which are involved in CDP synthesis...
November 30, 2016: Microbial Ecology
https://www.readbyqxmd.com/read/27857054/type-i-crispr-cas-targets-endogenous-genes-and-regulates-virulence-to-evade-mammalian-host-immunity
#11
Rongpeng Li, Lizhu Fang, Shirui Tan, Min Yu, Xuefeng Li, Sisi He, Yuquan Wei, Guoping Li, Jianxin Jiang, Min Wu
Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems in bacteria and archaea provide adaptive immunity against invading foreign nucleic acids. Previous studies suggest that certain bacteria employ their Type II CRISPR-Cas systems to target their own genes, thus evading host immunity. However, whether other CRISPR-Cas systems have similar functions during bacterial invasion of host cells remains unknown. Here we identify a novel role for Type I CRISPR-Cas systems in evading host defenses in Pseudomonas aeruginosa strain UCBPP-PA14...
December 2016: Cell Research
https://www.readbyqxmd.com/read/27836448/multilocus-amplicon-sequencing-of-pseudomonas-aeruginosa-cystic-fibrosis-airways-isolates-collected-prior-to-and-after-early-antipseudomonal-chemotherapy
#12
Sebastian Fischer, Leonie Greipel, Jens Klockgether, Marie Dorda, Lutz Wiehlmann, Nina Cramer, Burkhard Tümmler
BACKGROUND: Early antimicrobial chemotherapy can prevent or at least delay chronic cystic fibrosis (CF) airways infections with Pseudomonas aeruginosa. METHODS: During a 10-year study period P. aeruginosa was detected for the first time in 54 CF patients regularly seen at the CF centre Hannover. Amplicon sequencing of 34 loci of the P. aeruginosa core genome was performed in baseline and post-treatment isolates of the 15 CF patients who had remained P. aeruginosa - positive after the first round of antipseudomonal chemotherapy...
November 8, 2016: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/27834332/attenuation-of-quorum-sensing-regulated-behaviour-by-tinospora-cordifolia-extract-identification-of-its-active-constituents
#13
Viraj C Gala, Nithya R John, Ashok M Bhagwat, Ajit G Datar, Prashant S Kharkar, Krutika B Desai
BACKGROUND & OBJECTIVES: The pathogenicity of the nosocomial pathogens, Pseudomonas aeruginosa and Acinetobacter baumannii is regulated by their quorum sensing (QS) systems. The objective of the present study was to examine the effect of the cold ethyl acetate extract of Tinospora cordifolia stem on virulence and biofilm development in the wild type and clinical strains of P. aeruginosa and A. baumannii. The study was further aimed to identify the probable active constituents in the plant extract...
July 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/27825554/development-of-a-novel-series-of-non-natural-triaryl-agonists-and-antagonists-of-the-pseudomonas-aeruginosa-lasr-quorum-sensing-receptor
#14
Joseph N Capilato, Shane V Philippi, Thomas Reardon, Ashleigh McConnell, Dylan C Oliver, Amy Warren, Jill S Adams, Chun Wu, Lark J Perez
Bacterial chemical communication, through a process called quorum sensing (QS), plays a central role in infection in numerous bacterial pathogens. Quorum sensing in Pseudomonas aeruginosa employs a series of small molecule receptors including the master QS regulator, LasR. In this study we investigate a non-natural triaryl series of LasR ligands using a combination of structure activity relationship studies and computational modeling. These studies have enabled the identification of key structural requirements for ligand binding and have revealed a new strategy for inducing the therapeutically relevant antagonism of LasR...
January 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27781241/-laparoscopic-total-mesorectum-excision-with-the-guidance-of-membrane-anatomy
#15
Pan Chi
The efficacy of laparoscopic total mesorectum excision (TME) has been confirmed by many clinical trials and guidelines. But two issues on laparoscopic TME are still questioned, including the integrity of specimen membrane of TME and the incidence of postoperative sexual dysfunction. According to my experiences and the primary results of the multicenter clinical trial (LASRE, clinicaltrials.gov identifier: NCT01899547) conducted by me, the integrity of the specimen membrane of laparoscopic TME is not inferior to the open TME...
October 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27756565/purification-and-characterization-of-pseudomonas-aeruginosa-lasr-expressed-in-acyl-homoserine-lactone-free-escherichia-coli-cultures
#16
Andrés Corral Lugo, Abdelali Daddaoua, Alvaro Ortega, Bertrand Morel, Ana Isabel Díez Peña, Manuel Espinosa-Urgel, Tino Krell
Quorum sensing systems are essential for bacterial communication. We report here the purification and characterization of the Pseudomonas aeruginosa LasR quorum sensing regulator purified from lysates of E. coli cultures grown in the absence of added acyl-homoserine lactones (AHL). We show by isothermal titration calorimetry that LasR recognizes different AHLs with an affinity of approximately 1 μM. The affinity of LasR for its cognate 3-Oxo-C12-AHL was similar to that of other AHLs, indicating that this regulator has not evolved to preferentially recognize its cognate AHL...
October 15, 2016: Protein Expression and Purification
https://www.readbyqxmd.com/read/27713502/nutrient-reduction-induced-stringent-responses-promote-bacterial-quorum-sensing-divergence-for-population-fitness
#17
Kelei Zhao, Xikun Zhou, Wujiao Li, Xiuyue Zhang, Bisong Yue
Bacteria use a cell-cell communication system termed quorum-sensing (QS) to adjust population size by coordinating the costly but beneficial cooperative behaviors. It has long been suggested that bacterial social conflict for expensive extracellular products may drive QS divergence and cause the "tragedy of the commons". However, the underlying molecular mechanism of social divergence and its evolutionary consequences for the bacterial ecology still remain largely unknown. By using the model bacterium Pseudomonas aeruginosa PAO1, here we show that nutrient reduction can promote QS divergence for population fitness during evolution but requiring adequate cell density...
October 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27703072/lasr-variant-cystic-fibrosis-isolates-reveal-an-adaptable-quorum-sensing-hierarchy-in-pseudomonas-aeruginosa
#18
John B Feltner, Daniel J Wolter, Christopher E Pope, Marie-Christine Groleau, Nicole E Smalley, E Peter Greenberg, Nicole Mayer-Hamblett, Jane Burns, Eric Déziel, Lucas R Hoffman, Ajai A Dandekar
: Chronic Pseudomonas aeruginosa infections cause significant morbidity in patients with cystic fibrosis (CF). Over years to decades, P. aeruginosa adapts genetically as it establishes chronic lung infections. Nonsynonymous mutations in lasR, the quorum-sensing (QS) master regulator, are common in CF. In laboratory strains of P. aeruginosa, LasR activates transcription of dozens of genes, including that for another QS regulator, RhlR. Despite the frequency with which lasR coding variants have been reported to occur in P...
October 4, 2016: MBio
https://www.readbyqxmd.com/read/27678057/evidence-for-direct-control-of-virulence-and-defense-gene-circuits-by-the-pseudomonas-aeruginosa-quorum-sensing-regulator-mvfr
#19
Damien Maura, Ronen Hazan, Tomoe Kitao, Alicia E Ballok, Laurence G Rahme
Pseudomonas aeruginosa defies eradication by antibiotics and is responsible for acute and chronic human infections due to a wide variety of virulence factors. Currently, it is believed that MvfR (PqsR) controls the expression of many of these factors indirectly via the pqs and phnAB operons. Here we provide strong evidence that MvfR may also bind and directly regulate the expression of additional 35 loci across the P. aeruginosa genome, including major regulators and virulence factors, such as the quorum sensing (QS) regulators lasR and rhlR, and genes involved in protein secretion, translation, and response to oxidative stress...
September 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27650847/transcription-associated-mutation-of-lasr-in-pseudomonas-aeruginosa
#20
Chao Wang, John R McPherson, Lian-Hui Zhang, Steve Rozen, Kanaga Sabapathy
Pseudomonas aeruginosa is an opportunistic pathogen which infects cystic fibrosis and cancer patients with compromised immune systems. LasR is a master regulator which controls the virulence of P. aeruginosa in response to bacterial cell-density and host signals. During infection, lasR is frequently mutated, conferring P. aeruginosa a growth advantage in hosts and enhances resistance to widely used antibiotics. However, the mechanistic basis of lasR mutation is not well understood. We have tested here the hypothesis that transcription strength is a contributory determinant of lasR mutagenesis...
October 2016: DNA Repair
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