scholarly journals Functions Required for Extracellular Quinolone Signaling by Pseudomonas aeruginosa

2002 ◽  
Vol 184 (23) ◽  
pp. 6472-6480 ◽  
Author(s):  
Larry A. Gallagher ◽  
Susan L. McKnight ◽  
Marina S. Kuznetsova ◽  
Everett C. Pesci ◽  
Colin Manoil
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Secondary Metabolites ◽  
Regulatory Network ◽  
Biosynthetic Pathway ◽  
Extracellular Enzymes ◽  
Transcriptional Regulator ◽  
Transposon Mutagenesis ◽  
Sensing System ◽  
Quorum Sensing System

ABSTRACT A set of 30 mutants exhibiting reduced production of the phenazine poison pyocyanin were isolated following transposon mutagenesis of Pseudomonas aeruginosa PAO1. The mutants could be subdivided into those with defects in the primary phenazine biosynthetic pathway and those with more pleiotropic defects. The largest set of pleiotropic mutations blocked the production of the extracellular Pseudomonas quinolone signal (PQS), a molecule required for the synthesis of secondary metabolites and extracellular enzymes. Most of these pqs mutations affected genes which appear to encode PQS biosynthetic functions, although a transcriptional regulator and an apparent response effector were also represented. Two of the genes required for PQS synthesis (phnA and phnB) had previously been assumed to encode phenazine biosynthetic functions. The transcription of one of the genes required for PQS synthesis (PA2587/pqsH) was regulated by the LasI/R quorum-sensing system, thereby linking quorum sensing and PQS regulation. Others of the pleiotropic phenazine-minus mutations appear to inactivate novel components of the quorum-sensing regulatory network, including one regulator (np20) previously shown to be required for virulence in neutropenic mice.

scholarly journals Quorum-Sensing Regulation of a Copper Toxicity System in Pseudomonas aeruginosa

2010 ◽  
Vol 192 (10) ◽  
pp. 2557-2568 ◽  
Author(s):  
Joshua T. Thaden ◽  
Stephen Lory ◽  
Timothy S. Gardner
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Molecular Genetic ◽  
Copper Toxicity ◽  
Transcriptional Regulator ◽  
Global Gene Expression ◽  
Copper Resistance ◽  
Binding Motif ◽  
Sensing System ◽  
Quorum Sensing System

ABSTRACT The LasR/LasI quorum-sensing system in Pseudomonas aeruginosa influences global gene expression and mediates pathogenesis. In this study, we show that the quorum-sensing system activates, via the transcriptional regulator PA4778, a copper resistance system composed of 11 genes. The quorum-sensing global regulator LasR was recently shown to directly activate transcription of PA4778, a cueR homolog and a MerR-type transcriptional regulator. Using molecular genetic methods and bioinformatics, we verify the interaction of LasR with the PA4778 promoter and further demonstrate the LasR binding site. We also identify a putative PA4778 binding motif and show that the protein directly binds to and activates five promoters controlling the expression of 11 genes—PA3519 to -15, PA3520, mexPQ-opmE, PA3574.1, and cueA, a virulence factor in a murine model. Using gene disruptions, we show that PA4778, along with 7 of 11 gene targets of PA4778, increases the sensitivity of P. aeruginosa to elevated copper concentrations. This work identifies a cellular function for PA4778 and four other previously unannotated genes (PA3515, PA3516, PA3517, and PA3518) and suggests a potential role for copper in the quorum response. We propose to name PA4778 cueR.

scholarly journals Pseudomonas aeruginosa Regulatory Protein AnvM Controls Pathogenicity in Anaerobic Environments and Impacts Host Defense

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Yingchao Zhang ◽  
Chuan-min Zhou ◽  
Qinqin Pu ◽  
Qun Wu ◽  
Shirui Tan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Anaerobic Conditions ◽  
Content Type ◽  
Sensing System ◽  
Quorum Sensing System ◽  
Aerobic And Anaerobic ◽  
Aerobic And Anaerobic Conditions

ABSTRACT Pseudomonas aeruginosa, one of the most common pathogens in hospital-acquired infections, is tightly controlled by a multilayered regulatory network, including the quorum sensing system (QS), the type VI secretion system (T6SS), and resistance to host immunity. We found that the P. aeruginosa 3880 (PA3880) gene, which encodes an unknown protein, acts as a regulator of anaerobic metabolism in response to oxidative stress and virulence in P. aeruginosa. More than 30 PA3880 homologs were found in other bacterial genomes, indicating that PA3880 is widely distributed in the Bacteria kingdom as a highly conserved gene. Deletion of the PA3880 gene changed the expression levels of more than 700 genes, including a group of virulence genes, under both aerobic and anaerobic conditions. To further study the mechanisms of PA3880-mediated regulation in virulence, we utilized a bacterial two-hybrid assay and found that the PA3880 protein interacted directly with QS regulator MvfR and anaerobic regulator Anr. Loss of the PA3880 protein significantly blunted the pathogenicity of P. aeruginosa, resulting in increased host survival, decreased bacterial burdens, reduced inflammatory responses, and fewer lung injuries in challenged mice hosts. Mechanistically, we found that Cys44 was a critical site for the full function of PA3880 in influencing alveolar macrophage phagocytosis and bacterial clearance. We also found that AnvM directly interacted with host receptors Toll-like receptor 2 (TLR2) and TLR5, which might lead to activation of the host immune response. Hence, we gave the name AnvM (anaerobic and virulence modulator) to the PA3880 protein. This characterization of AnvM could help to uncover new targets and strategies to treat P. aeruginosa infections. IMPORTANCE Infections by Pseudomonas aeruginosa, one of the most frequently isolated human pathogens, can create huge financial burdens. However, knowledge of the molecular mechanisms involved in the pathogenesis of P. aeruginosa remains elusive. We identified AnvM as a novel regulator of virulence in P. aeruginosa. Deletion of anvM altered the expression levels of more than 700 genes under aerobic and anaerobic conditions, including quorum sensing system genes and oxidative stress resistance genes. AnvM directly interacted with MvfR and Anr, thus regulating their downstream genes. More importantly, AnvM directly bound to TLR2 and TLR5, which turn on the host immune response. These findings provide insights into the significance of AnvM homologs in pathogenic bacteria and suggest a potential drug target against bacterial infection.

scholarly journals Mutation of pfm affects the adherence of Pseudomonas aeruginosa to host cells and the quorum sensing system

2011 ◽  
Vol 324 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Rui Mou ◽  
Fang Bai ◽  
Qiaonan Duan ◽  
Xuehan Wang ◽  
Haijin Xu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Host Cells ◽  
Sensing System ◽  
Quorum Sensing System

scholarly journals RsaL, a Novel Repressor of Virulence Gene Expression in Pseudomonas aeruginosa

1999 ◽  
Vol 181 (7) ◽  
pp. 2175-2184 ◽  
Author(s):  
Teresa de Kievit ◽  
Patrick C. Seed ◽  
Jonathon Nezezon ◽  
Luciano Passador ◽  
Barbara H. Iglewski
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Determinants ◽  
Protein Fusion ◽  
Elastase Activity ◽  
Virulence Gene Expression ◽  
Sensing System ◽  
Repressive Effect ◽  
Quorum Sensing System ◽  
Pai 1

ABSTRACT As components of a Pseudomonas aeruginosaquorum-sensing system, LasR and PAI-1 globally regulate expression of multiple virulence determinants, as well as the second P. aeruginosa quorum-sensing system. To date, no information exists on negative regulation of the quorum-sensing cascade in P. aeruginosa. Here we describe a novel gene, rsaL, which is located downstream from lasR and transcribed antisense relative to lasR. In P. aeruginosa,overexpression of rsaL results in reduced lasBexpression and decreased elastase activity. With the use of a six-His protein fusion system, we demonstrate that rsaL encodes an 11-kDa protein. Direct quantitation of PAI-1 levels in cultures and studies utilizing Escherichia coli lambda lysogens carryinglacZ transcriptional fusions reveal that RsaL specifically represses transcription of the PAI-1 autoinducer synthase gene,lasI. RsaL’s repressive effect on lasI and the associated decrease in elastase activity have important implications for the expression of all LasR–PAI-1-dependent virulence genes and the overall pathogenicity of P. aeruginosa.

scholarly journals Effects of Allicin on the Formation of Pseudomonas aeruginosa Biofilm and the Production of Quorum-Sensing Controlled Virulence Factors

2013 ◽  
Vol 62 (3) ◽  
pp. 243-251 ◽  
Author(s):  
LIN LIHUA ◽  
WANG JIANHUI ◽  
YU JIALIN ◽  
LI YAYIN ◽  
LIU GUANXIN
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Bacterial Pathogen ◽  
Organosulfur Compound ◽  
Extracellular Polysaccharide ◽  
Sensing System ◽  
Quorum Sensing System ◽  
Extracellular Polysaccharide Substances ◽  
Multiple Antibiotics

The Gram-negative Pseudomonas aeruginosa bacterial pathogen is reputed for its resistance to multiple antibiotics, and this property is strongly associated with the development of biofilms. Bacterial biofilms form by aggregation of microorganisms on a solid surface and secretion of an extracellular polysaccharide substances that acts as a physical protection barrier for the encased bacteria. In addition, the P aeruginosa quorum-sensing system contributes to antibiotic resistance by regulating the expression of several virulence factors, including exotoxin A, elastase, pyoverdin and rhamnolipid. The organosulfur compound allicin, derived from garlic, has been shown to inhibit both surface-adherence of bacteria and production of virulence factors. In this study, the effects of allicin on P aeruginosa biofilm formation and the production of quorum-sensing controlled virulence factors were investigated. The results demonstrated that allicin could inhibit early bacterial adhesion, reduce EPS secretion, and down-regulate virulence factors' production. Collectively, these findings suggest the potential of allicin as a therapeutic agent for controlling P aeruginosa biofilm.

scholarly journals Evaluation of the Antibacterial and Investigation of the Molecular Docking of New Derivatives of 1, 3, 4-Oxadiazole as Inhibitors of Quorum Sensing System in the Human Pathogen Pseudomonas Aeruginosa

2021 ◽  
Vol 8 (1) ◽  
pp. 27-33
Author(s):  
Sepideh Ghameshlouei ◽  
Nakisa Zarrabi Ahrabi ◽  
Ali Souldozi ◽  
Yasin SarveAhrabi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Molecular Docking ◽  
Quorum Sensing ◽  
Regulatory Protein ◽  
Inhibitory Effect ◽  
Chemical Structures ◽  
Sensing System ◽  
Wide Range ◽  
Quorum Sensing System ◽  
Derivatives Of

Background: Oxadiazoles are a group of anti-inflammatory compounds that have a wide range of activity due to their higher efficacy. Pseudomonas aeruginosa is an opportunistic pathogen and a major pathogen of nosocomial infections. This study aimed to evaluate the antibacterial and investigation of the molecular docking of new derivatives of 1, 3, 4-oxadiazole against P. aeruginosa, in vitro & in silico. Materials and Methods: Four new derivatives were synthesized and added to our previous synthetic derivatives of 1, 3, 4-oxadiazole. The antibacterial activity of all derivatives was measured based on three standard species of P. aeruginosa using inhibition zone (IZ) and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods. Then, employing the computational design of the drug by the molecular docking method, the inhibitory effect of synthetic compounds on the LasR regulatory protein of P. aeruginosa quorum sensing system was investigated, which plays an important role in regulating the expression of pathogenic genes in bacteria. Results: The chemical structures of new compounds were characterized by IR spectra and 1H-NMR. A variety of inhibitory effects were observed by the synthesized compounds – compound 4d and 4g, in particular. Also, the inhibitory effect of these two compounds on the LasR regulatory protein under the control of the quorum sensing system in P. aeruginosa was demonstrated by molecular docking. Conclusions: The results of this study showed that the two compounds containing the functional group of naphthalene and fluorophenyl have a significant effect on the inhibition of P. aeruginosa, as well as on the LasR protein of this bacterium.

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