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Huicong Yan, Meizhen Wang, Feng Sun, Ajai A Dandekar, Dongsheng Shen, Na Li
Pseudomonas aeruginosa uses quorum sensing (QS) to regulate the production of public goods such as the secreted protease elastase. P. aeruginosa requires the LasI-LasR QS circuit to induce elastase and enable growth on casein as the sole carbon and energy source. The LasI-LasR system also induces a second QS circuit, the RhlI-RhlR system. During growth on casein, LasR-mutant social cheaters emerge, and this can lead to a population collapse. In a minimal medium containing ammonium sulfate as a nitrogen source, populations do not collapse, and cheaters and cooperators reach a stable equilibrium; however, without ammonium sulfate, cheaters overtake the cooperators and populations collapse...
2018: Frontiers in Microbiology
Jobina Rajkumari, Subhomoi Borkotoky, Ayaluru Murali, Kitlangki Suchiang, Saswat Kumar Mohanty, Siddhardha Busi
The production of virulence determinants and biofilm formation in numerous pathogens is regulated by the cell-density-dependent phenomenon, Quorum sensing (QS). The QS system in multidrug resistant opportunistic pathogen, P. aeruginosa constitutes of three main regulatory circuits namely Las, Rhl, and Pqs which are closely linked to its pathogenicity and establishment of chronic infections. In spite intensive antibiotic therapy, P. aeruginosa continue to be an important cause of nosocomial infections and also the major cause of mortality in Cystic Fibrosis patients with 80% of the adults suffering from chronic P...
March 8, 2018: Microbial Pathogenesis
Manmohit Kalia, Vivek Kumar Yadav, Pradeep Kumar Singh, Deepmala Sharma, Shahid Suhail Narvi, Vishnu Agarwal
AIMS: Pseudomonas aeruginosa is a well-known pathogen responsible for various infections due to its capability to develop biofilm and various virulent phenotypes that are regulated by quorum sensing. Pathogenesis of the bacteria may be halted by interfering with the signaling molecules and the quorum sensing receptors. Therefore, the present study explores the potential of parthenolide, a sesquiterpene lactone of feverfew plant, as a promising candidate against P. aeruginosa PAO1 associated virulence factors and biofilm...
March 7, 2018: Life Sciences
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
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
Christina L Wysoczynski-Horita, Michelle E Boursier, Ryan Hill, Kirk Hansen, Helen E Blackwell, Mair E A Churchill
Pseudomonas aeruginosa is an opportunistic pathogen that uses the process of quorum sensing (QS) to coordinate the expression of many virulence genes. During quorum sensing, N-acyl-homoserine lactone (AHL) signaling molecules regulate the activity of three LuxR-type transcription factors, LasR, RhlR, and QscR. To better understand P. aeruginosa QS signal reception, we examined the mechanism underlying the response of QscR to synthetic agonists and antagonists using biophysical and structural approaches. The structure of QscR bound to a synthetic agonist reveals a novel mode of ligand binding supporting a general mechanism for agonist activity...
February 13, 2018: Molecular Microbiology
Maria-Eleni K Stathopoulou, Christina N Banti, Nikolaos Kourkoumelis, Antonios G Hatzidimitriou, Angelos G Kalampounias, Sotiris K Hadjikakou
The known metallotherapeutic [Ag(salH)]2 (AGSAL-1) of salicylic acid (salH2), was used for the development of new efficient silver based material for wounds healing. AGSAL-1 was characterized by spectroscopic techniques and X-ray crystallography. The wound healing epithelialization of AGSAL-1 was investigated by the means of scratch assay against immortalized human keratinocytes (HaCaT) cells. The anti-inflammatory activity of AGSAL-1 was evaluated by monitoring the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX)...
February 1, 2018: Journal of Inorganic Biochemistry
Jin-Wei Zhou, Huai-Zhi Luo, Huan Jiang, Ting-Kun Jian, Zi-Qian Chen, Ai-Qun Jia
The quorum sensing (QS) inhibitory activity of hordenine from sprouting barley against foodborne pathogen Pseudomonas aeruginosa was evaluated for the first time here. At concentrations ranging from 0.5 to 1.0 mg mL-1, hordenine inhibited the levels of acyl-homoserine lactones (AHLs). The enhanced susceptibility of hordenine with netilmicin on P. aeruginosa PAO1 biofilm formation as well as their efficiency in disrupting preformed biofilms was also evaluated using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM)...
January 21, 2018: Journal of Agricultural and Food Chemistry
July Fong, Chaodong Zhang, Renliang Yang, Zhao Zhi Boo, Soon Keat Tan, Thomas E Nielsen, Michael Givskov, Xue-Wei Liu, Wu Bin, Haibin Su, Liang Yang
The threat of antibiotic resistant bacteria has called for alternative antimicrobial strategies that would mitigate the increase of classical resistance mechanism. Many bacteria employ quorum sensing (QS) to govern the production of virulence factors and formation of drug-resistant biofilms. Targeting the mechanism of QS has proven to be a functional alternative to conventional antibiotic control of infections. However, the presence of multiple QS systems in individual bacterial species poses a challenge to this approach...
January 18, 2018: Scientific Reports
Ye Chen, Joanne M L Ho, David L Shis, Chinmaya Gupta, James Long, Daniel S Wagner, William Ott, Krešimir Josić, Matthew R Bennett
One challenge for synthetic biologists is the predictable tuning of genetic circuit regulatory components to elicit desired outputs. Gene expression driven by ligand-inducible transcription factor systems must exhibit the correct ON and OFF characteristics: appropriate activation and leakiness in the presence and absence of inducer, respectively. However, the dynamic range of a promoter (i.e., absolute difference between ON and OFF states) is difficult to control. We report a method that tunes the dynamic range of ligand-inducible promoters to achieve desired ON and OFF characteristics...
January 4, 2018: Nature Communications
David W Basta, Megan Bergkessel, Dianne K Newman
Microbial growth arrest can be triggered by diverse factors, one of which is energy limitation due to scarcity of electron donors or acceptors. Genes that govern fitness during energy-limited growth arrest and the extent to which they overlap between different types of energy limitation are poorly defined. In this study, we exploited the fact that Pseudomonas aeruginosa can remain viable over several weeks when limited for organic carbon (pyruvate) as an electron donor or oxygen as an electron acceptor. ATP values were reduced under both types of limitation, yet more severely in the absence of oxygen...
November 28, 2017: MBio
Émilie Maillé, Manon Ruffin, Damien Adam, Hatem Messaoud, Shantelle L Lafayette, Geoffrey McKay, Dao Nguyen, Emmanuelle Brochiero
The function of cystic fibrosis transmembrane conductance regulator (CFTR) channels is crucial in human airways. However unfortunately, chronic Pseudomonas aeruginosa infection has been shown to impair CFTR proteins in non-CF airway epithelial cells (AEC) and to alter the efficiency of new treatments with CFTR modulators designed to correct the basic CFTR default in AEC from cystic fibrosis (CF) patients carrying the F508del mutation. Our aim was first to compare the effect of laboratory strains, clinical isolates, engineered and natural mutants to determine the role of the LasR quorum sensing system in CFTR impairment, and second, to test the efficiency of a quorum sensing inhibitor to counteract the deleterious impact of P...
2017: Frontiers in Cellular and Infection Microbiology
Hyunsuk Choi, So-Young Ham, Eunji Cha, Yujin Shin, Han-Shin Kim, Jeong Kyu Bang, Sang-Hyun Son, Hee-Deung Park, Youngjoo Byun
Pseudomonas aeruginosa is a causative agent of chronic infections in immunocompromised patients. Disruption of quorum sensing circuits is an attractive strategy for treating diseases associated with P. aeruginosa infection. In this study, we designed and synthesized a series of gingerol analogs targeting LasR, a master regulator of quorum sensing networks in P. aeruginosa. Structure-activity relationship studies showed that a hydrogen-bonding interaction in the head section, stereochemistry and rotational rigidity in the middle section, and optimal alkyl chain length in the tail section are important factors for the enhancement of LasR-binding affinity and for the inhibition of biofilm formation...
December 14, 2017: Journal of Medicinal Chemistry
Giordano Rampioni, Giulia Giallonardi, Francesca D'Angelo, Livia Leoni
Quorum sensing (QS) is recognized as a promising target for the identification of anti-virulence drugs hampering Pseudomonas aeruginosa adaptability to the host environment and pathogenicity. Consequently, a number of studies in the last decade focused on the identification of small molecules or proteins with anti-QS activity, mainly targeting the las QS system, which is based on N-3-oxododecanoyl-homoserine lactone (3OC12-HSL) as signal molecule. Different experimental approaches have been successfully used to identify QS blockers interfering with the activity/stability of the 3OC12-HSL receptor LasR, with the functionality of the 3OC12-HSL synthase LasI, or with the stability/bioavailability of the 3OC12-HSL signal molecule itself...
2018: Methods in Molecular Biology
Kasturi Ganesh Barki, Amitava Das, Sriteja Dixith, Piya Das Ghatak, Shomita Mathew-Steiner, Elizabeth Schwab, Savita Khanna, Daniel J Wozniak, Sashwati Roy, Chandan K Sen
OBJECTIVE: This study was designed to employ electroceutical principles, as an alternative to pharmacological intervention, to manage wound biofilm infection. Mechanism of action of a United States Food and Drug Administration-cleared wireless electroceutical dressing (WED) was tested in an established porcine chronic wound polymicrobial biofilm infection model involving inoculation with Pseudomonas aeruginosa PAO1 and Acinetobacter baumannii 19606. BACKGROUND: Bacterial biofilms represent a major wound complication...
November 2, 2017: Annals of Surgery
Syed Ghazanfar Ali, Mohammad Azam Ansari, Qazi Mohd Sajid Jamal, Haris M Khan, Mohammad Jalal, Hilal Ahmad, Abbas Ali Mahdi
Pseudomonas aeruginosa an opportunistic pathogen regulates its virulence through Quorum sensing (QS) mechanism comprising of Las and Rhl system. Targeting of QS mechanism could be an ideal strategy to combat infection caused by P . aeruginosa . Silver nanoparticles (AgNPs) have been broadly applied as antimicrobial agents against a number of pathogenic bacterial and fungal strains, but have not been reported as an anti-QS agent. Therefore, the aim of present work was to show the computational analysis for the interaction of AgNPs with the QS system using an In silico approach...
2017: In Silico Pharmacology
Hongdong Li, Xingyuan Li, Chao Song, Yunhui Zhang, Zhengli Wang, Zhenqiu Liu, Hong Wei, Jialin Yu
Bacterial communication systems, such as quorum sensing (QS), have provided new insights of alternative approaches in antimicrobial treatment. We recently reported that one QS signal, named as autoinducer-2 (AI-2), can affect the behaviors of Pseudomonas aeruginosa PAO1 in a dose-dependent manner. In this study, we aimed to investigate the effects of AI-2 on P. aeruginosa PAO1 biofilm formation and virulence factors production in vitro, and in vivo using a pulmonary infection mouse model. Exogenous AI-2 resulted in increased biofilms architecture, the number of viable cells, and the yield of pyocyanin and elastase virulence factors in wild type P...
2017: Frontiers in Microbiology
Bulent M Ertugrul, Erman Oryasin, Benjamin A Lipsky, Ayşe Willke, Bulent Bozdogan
BACKGROUND: Outcomes of antibiotic treatment of diabetic foot infections (DFIs) may depend not only on the antimicrobial susceptibility of the aetiologic agents, but also their ability to produce virulence factors. This study aimed to use polymerase chain reaction (PCR) with specific primers to investigate the presence of virulence genes among isolates of Pseudomonas aeruginosa isolates cultured from specimens from diabetic foot and other infections. METHODS: We examined 63 P...
October 27, 2017: Infectious Diseases
Yinqiu Xu, Xupeng Tong, Pinghua Sun, Leming Bi, Kejiang Lin
AIM: Resistance to conventional antibiotics has spurred interest in exploring new antimicrobial strategies. Suppressing quorum sensing within biofilm is a promising antimicrobial strategy. LasR in quorum sensing system of the Gram-negative bacteria, Pseudomonas aeruginosa, directly enhances virulence and antibiotic resistance, with QscR as its indirect suppressor, so targeting both of them can synergistically take the effect. METHODOLOGY/RESULTS: An in silico protocol combining pharmacophores with molecular docking was applied...
November 2017: Future Medicinal Chemistry
Malabika Banerjee, Soumitra Moulick, Kunal Kumar Bhattacharya, Debaprasad Parai, Subrata Chattopadhyay, Samir Kumar Mukherjee
Quorum-sensing (QS) is known to play an essential role in regulation of virulence factors and toxins during Pseudomonas aeruginosa infection which may frequently cause antibiotic resistance and hostile outcomes of inflammatory injury. Therefore, it is an urgent need to search for a novel agent with low risk of resistance development that can target QS and inflammatory damage prevention as well. Andrographis paniculata, a herbaceous plant under the family Acanthaceae, native to Asian countries and also cultivated in Scandinavia and some parts of Europe, has a strong traditional usage with its known antibacterial, anti-inflammatory, antipyretic, antiviral and antioxidant properties...
December 2017: Microbial Pathogenesis
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