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Kyle C Costa, Leon S Moskatel, Lucas A Meirelles, Dianne K Newman
Phenazines are a class of bacterially-produced redox-active metabolites that are found in natural, industrial, and clinical environments. In Pseudomonas spp., phenazine-1-carboxylic acid (PCA)--the precursor of all phenazine metabolites--facilitates nutrient acquisition, biofilm formation, and competition with other organisms. While the removal of phenazines negatively impacts these activities, little is known about the genes or enzymes responsible for phenazine degradation by other organisms. Here, we report that the first step of PCA degradation by Mycobacterium fortuitum is catalyzed by a [underln]ph[/underln]enazine [underln]d[/underln]egrading decarboxylase (PhdA)...
February 26, 2018: Journal of Bacteriology
Debaprasad Parai, Malabika Banerjee, Pia Dey, Arindam Chakraborty, Ekramul Islam, Samir Kumar Mukherjee
This study aimed to evaluate the effect of reserpine, a plant-derived indole-alkaloid, against Pseudomonas aeruginosa PAO1 biofilms. The anti-biofilm activity of reserpine was evaluated by crystal violet staining, MTT assay, confocal laser scanning microscopy and scanning electron microscopy. Reserpine effects were also assessed by qRT-PCR of quorum sensing (QS)-regulated genes and biochemical quantification of the QS-mediated virulence factors pyocyanin, rhamnolipids, proteases and elastases. Reserpine reduced biofilm formation, cell motility, virulence factor production, and QS-controlled gene expression...
February 27, 2018: Biofouling
Jan Leipert, Ingrid Bobis, Sabine Schubert, Helmut Fickenscher, Matthias Leippe, Andreas Tholey
The identification and quantification of molecules involved in bacterial communication are major prerequisites for the understanding of interspecies interactions at the molecular level. We developed a procedure allowing the determination of 2-heptyl-4(1H)-quinolone (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS) and the virulence factor pyocyanin (PYO) formed by the Gram-negative bacterium Pseudomonas aeruginosa. The method is based on dispersive liquid-liquid microextraction from small supernatant volumes (below 10 μL) followed by quantitative matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS)...
February 22, 2018: Analytical and Bioanalytical Chemistry
Alison A Jack, Saira Khan, Lydia C Powell, Manon F Pritchard, Konrad Beck, Hina Sadh, Lucy Sutton, Alessandra Cavaliere, Hannah Florance, Philip D Rye, David W Thomas, Katja E Hill
Pseudomonas aeruginosa plays a major role in many chronic infections. Its ability to readily form biofilms contributes to its success as an opportunistic pathogen and its resistance/tolerance to antimicrobial/antibiotic therapy. A low molecular weight alginate oligomer (OligoG CF-5/20), derived from marine algae, has previously been shown to impair motility in P. aeruginosa biofilms and disrupt pseudomonal biofilm assembly. As these bacterial phenotypes are regulated by quorum sensing (QS), we hypothesized that OligoG CF-5/20 may induce alterations in QS signalling in P...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Jai-Nien Tung, Po-Lin Lin, Yao-Chen Wang, De-Wei Wu, Chi-Yi Chen, Huei Lee
Programmed death ligand (PD-L1) expression was associated with tumor immune escape and subsequent poor prognosis in non-small cell lung cancer (NSCLC). This expression was higher in patients with EGFR-mutated NSCLC tumors than in those with EGFR-wild-type (WT) NSCLC tumors. We therefore hypothesized that poor prognosis mediated by higher PD-L1 may be partially through conferring resistance to tyrosine kinase inhibitor (TKI) in NSCLC regardless of EGFR mutation. The change in PD-L1 expression following gene manipulation corresponded with changes in expression of HIF-1α and YAP1...
January 12, 2018: Oncotarget
Yi-Ling Lo, Chyi-Liang Chen, Lunda Shen, Ying-Ching Chen, Yi-Hsin Wang, Chung-Chan Lee, Lian-Chen Wang, Chih-Hsien Chuang, Rajendra Prasad Janapatla, Cheng-Hsun Chiu, Hwan-You Chang
FliA is known to be a sigma factor that regulates bacterial flagella gene expression. Accumulating evidence suggests that FliA is involved in bacterial behavior other than motility. To elucidate the contribution of FliA to Pseudomonas aeruginosa pathophysiology, we analyzed the biological properties and gene expression profiles of a ΔfliA mutant. Transcriptome analysis results demonstrated that the expression levels of flagella biogenesis genes decreased dramatically in the mutant; consequently, the ΔfliA mutant failed to synthesize flagella and exhibited reduced motility...
February 9, 2018: Research in Microbiology
Xiaochun Chen, Jianwei Chen, Yinchun Yan, Su Chen, Xuewei Xu, Huawei Zhang, Hong Wang
In this study, three active compounds isolated from Oceanobacillus sp. XC22919 were identified as 2-methyl-N-(2'-phenylethyl) butyramide (1), 3-methyl-N-(2'-phenylethyl)-butyramide (2) and benzyl benzoate (3), and were first reported to exhibit the apparent quorum sensing inhibitory activities against C. violaceum 026 and P. aeruginosa. Compounds 1-3 inhibited violacein production of C. violaceum 026 by 10.5-55.7, 11.2-55.7, and 27.2%-95.7%, respectively, and inhibited pyocyanin production of P. aeruginosa by 1...
February 12, 2018: Natural Product Research
Sebastian Virreira Winter, Arturo Zychlinsky
Inflammasomes are cytosolic complexes that mature and secrete the inflammatory cytokines IL-1β and IL-18 and induce pyroptosis. The NLRP3 inflammasome detects many pathogen- and danger-associated molecular patterns, and reactive oxygen/nitrogen species (ROS/RNS) have been implicated in its activation. The phenazine pyocyanin (PCN) is a virulence factor of Pseudomonas aeruginosa and generates superoxide in cells. Here, we report that PCN inhibits IL-1β and IL-18 release and pyroptosis upon NLRP3 inflammasome activation in macrophages by preventing speck formation and Caspase-1 maturation...
February 6, 2018: Journal of Biological Chemistry
Felix LewisOscar, Chari Nithya, Sulaiman Ali Alharbi, Naiyf S Alharbi, Nooruddin Thajuddin
Biofilm forming pathogenic bacteria showing resistance towards antimicrobial agents has increased the urge to find an alternative treatment strategy. Among the biofilm forming pathogenic bacteria, Pseudomonas aeruginosa is a well-recognised Gram negative biofilm former causing nosocomial infection and other disease among immunocompromised patients. The aim of the current study is to evaluate the antipathogenic potentials of S. platensis against P. aeruginosa. S. platensis methanolic extract (SME) inhibited the biofilm (89%), extracellular polymeric substances (EPS), cell surface hydrophobicity (CSH) (44%), pyocyanin, pyoveridin and swarming motility of P...
January 31, 2018: Microbial Pathogenesis
Bai-Min Lai, Hui-Cong Yan, Mei-Zhen Wang, Na Li, Dong-Sheng Shen
In the bacterium Pseudomonas aeruginosa, the synthesis and secretion of extracellular protease is a typical cooperative behavior regulated by quorum sensing. However, this type of cooperative behavior is easily exploited by other individuals who do not synthesize public goods, which is known as the "tragedy of the commons". Here P. aeruginosa was inoculated into casein media with different nitrogen salts added. In casein broth, protease (a type of public good) is necessary for bacterial growth. After 30 days of sequential transfer, some groups propagated stably and avoided "tragedy of the commons"...
February 2018: Journal of Microbiology / the Microbiological Society of Korea
Alexander S Little, Yuta Okkotsu, Alexandria A Reinhart, F Heath Damron, Mariette Barbier, Brandon Barrett, Amanda G Oglesby-Sherrouse, Joanna B Goldberg, William L Cody, Michael J Schurr, Michael L Vasil, Michael J Schurr
Pseudomonas aeruginosa employs numerous, complex regulatory elements to control expression of its many virulence systems. The P. aeruginosa AlgZR two-component regulatory system controls the expression of several crucial virulence phenotypes. We recently determined, through transcriptomic profiling of a PAO1 ΔalgR mutant strain compared to wild-type PAO1, that algZR and hemCD are cotranscribed and show differential iron-dependent gene expression. Previous expression profiling was performed in strains without algR and revealed that AlgR acts as either an activator or repressor, depending on the gene...
January 30, 2018: MBio
Fadi Soukarieh, Eduard Vico Oton, Jean-Frédéric Dubern, Janice Gomes, Nigel Halliday, Maria de Pilar Crespo, Jonathan Ramírez-Prada, Braulio Insuasty, Rodrigo Abonia, Jairo Quiroga, Stephan Heeb, Paul Williams, Michael J Stocks, Miguel Cámara
Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis, wound and nosocomial infections, posing a serious burden to public health, due to its antibiotic resistance. The P. aeruginosa Pseudomonas Quinolone System (pqs) quorum sensing system, driven by the activation of the transcriptional regulator, PqsR (MvfR) by alkylquinolone (AQ) signal molecules, is a key player in the regulation of virulence and a potential target for the development of novel antibacterial agents. In this study, we performed in silico docking analysis, coupled with screening using a P...
January 28, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Fadilah Sfouq Aleanizy, Fulwah Yahya Alqahtani, Gamal Shazly, Rihaf Alfaraj, Ibrahim Alsarra, Aws Alshamsan, Hosam Gareeb Abdulhady
Objective: The purpose of this study was to study the antimicrobial activity of chitosan nanoparticles (CSNPs) on Pseudomonas aeruginosa with special emphasis on their sensitivity to pH and the effect of pH on their activity. Methodology: Antimicrobial activity of CSNPs against Pseudomonas aeruginosa at different pH was tested using broth dilution method. Further assessment of antivirulence activity and sensitization of CSNPs on Pseudomonas aeruginosa were examined...
January 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Jun Mao, Alexander Zaborin, Valeriy Poroyko, David Goldfeld, Nathaniel A Lynd, Wei Chen, Matthew V Tirrell, Olga Zaborina, John C Alverdy
Phosphate is a key and universal "cue" in response to which bacteria either enhance their virulence when local phosphate is scarce or downregulate it when phosphate is adundant. Phosphate becomes depleted in the mammalian gut following physiologic stress and serves as a major trigger for colonizing bacteria to express virulence. This process cannot be reversed with oral supplementation of inorganic phosphate because it is nearly completely absorbed in the proximal small intestine. In the present study, we describe the de novo synthesis of phosphorylated polyethylene glycol compounds with three defined ABA (hydrophilic/-phobic/-philic) structures, ABA-PEG10k-Pi10, ABA-PEG16k-Pi14, and ABA-PEG20k-Pi20, and linear polymer PEG20k-Pi20 absent of the hydrophobic block...
September 11, 2017: ACS Biomaterials Science & Engineering
Devinder Arora, Susan Hall, Shailendra Anoopkumar-Dukie, Rachel Morrison, Amelia McFarland, Anthony V Perkins, Andrew K Davey, Gary D Grant
Pyocyanin (PCN) is a virulence factor secreted by Pseudomonas aeruginosa (P. aeruginosa) that has been shown to have numerous toxic effects in both in vitro and in vivo studies. Such toxicities include pro-inflammatory and pro-oxidant mediated responses. It is hypothesized that PCN can cross biological membranes and reach the systemic circulation but no previous studies have investigated this. The aim of this study was, therefore, to quantify PCN in plasma and assess if systemic responses were occurring after localized intranasal administration in C57BL/6J mice...
January 16, 2018: Toxicology Mechanisms and Methods
Shengrong Li, Siyu Chen, Jilin Fan, Zhen Cao, Weihao Ouyang, Ning Tong, Xin Hu, Jie Hu, Peishan Li, Zifeng Feng, Xi Huang, Yuying Li, Mingshan Xie, Ruikun He, Jingyi Jian, Biyuan Wu, Chen Xu, Weijian Wu, Jialiang Guo, Jing Lin, Pinghua Sun
IQS has been proven to be a new quorum sensing (QS) system against bacterial biofilm formation, which is activated in the common phosphate-limiting environment of infected tissues taking over the central las system. Up to now, numerous biofilm inhibitors which function by affecting traditional QS system have been reported. However, no compound has been reported to exert anti-biofilm activity through IQS system. Herein, various novel IQS derivatives were synthesized by the reaction of thiazole-4-carboxylic acid with different linear alcohols (R-OH) or amines (R-NH2)...
December 27, 2017: European Journal of Medicinal Chemistry
P Sankar Ganesh, V Ravishankar Rai
Pseudomonas aeruginosa use small signaling molecules such as acyl homoserine lactones (AHLs), which play an important role in release virulence factors and toxin for further establishment of host infection. Thus, involving with the QS system would provide alternative ways of preventing the pathogenicity. In the present study, totally six medicinal plants (Terminalia bellerica, Celastrus paniculatus, Kingiodendron pinnatum, Schleichera oleosa, Melastoma malabathricum, Garcinia gummi-gutta) were screened for anti-QS activity using biomonitor strain of Chromobacterium violaceum CV12472...
January 2018: Journal of Traditional and Complementary Medicine
Manoj Kushwaha, Shreyans K Jain, Nisha Sharma, Vidushi Abrol, Sundeep Jaglan, Ram A Vishwakarma
Targeting the main three networking systems viz. Las, RhI and PQS via natural quenchers is a new ray of hope for combating the persistent behavior of Pseudomonas aeruginosa. In the bacterial chemical vocabulary pyocyanin, N-AHLs and rhamnolipids are the main keywords, which are responsible for the social and nomadic behavior of P. aeruginosa. In the present work LCMS-based real-time qualitative and quantitative analysis of pyocyanin, green phenazine, N-AHLs, and rhamnolipids were performed. The quantitative analysis indicates that the production of pyocyanin and NHSLs increases with time while the production of rhamnolipids discontinued after 16 Hrs...
January 5, 2018: ACS Chemical Biology
Aylin Moayedi, Jamileh Nowroozi, Abbas Akhavan Sepahy
Objectives: Pyocyanin is a blue-greenish redox-active pigment, produced by Pseudomonas aeruginosa, with a wide range of biological and biotechnological applications. Pyocyanin biosynthesis is regulated by the quorum-sensing (QS) system in which the expression of QS genes and QS-controlled virulence genes may be affected by serum as a complex medium. In the current study, effects of adult bovine serum (ABS) and fetal bovine serum (FBS) on the production of pyocyanin were examined in order to develop it...
December 2017: Iranian Journal of Basic Medical Sciences
Siti N Fatin, Tan Boon-Khai, Alexander Chong Shu-Chien, Melati Khairuddean, Amirul Al-Ashraf Abdullah
The resistance of Pseudomonas aeruginosa to conventional antimicrobial treatment is a major scourge in healthcare. Therefore, it is crucial that novel potent anti-infectives are discovered. The aim of the present study is to screen marine actinomycetes for chemical entities capable of overcoming P. aeruginosa infection through mechanisms involving anti-virulence or host immunity activities. A total of 18 actinomycetes isolates were sampled from marine sediment of Songsong Island, Kedah, Malaysia. Upon confirming that the methanolic crude extract of these isolates do not display direct bactericidal activities, they were tested for capacity to rescue Caenorhabditis elegans infected with P...
2017: Frontiers in Microbiology
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