Review
Chemistry, Medicinal
Qiaoqiang Li, Shen Mao, Hong Wang, Xinyi Ye
Summary: The survival pressure caused by antibiotics prompts bacteria to develop drug resistance. Quorum sensing is an intercellular communication system that regulates bacterial virulence and biofilm formation. In Pseudomonas aeruginosa, the formation and diffusion of biofilm is closely related to the quorum sensing system. Quorum-sensing inhibitors can reduce bacterial toxicity and enhance sensitivity to antibiotics, making them a popular topic for research and development in anti-infection. This review provides an overview of the Pseudomonas aeruginosa quorum-sensing system and quorum-sensing inhibitors research, which will aid in the future development of novel inhibitors.
Review
Chemistry, Medicinal
Mohammad Anwar Hossain, Nadezhda A. German
Summary: In recent years, modulators of quorum sensing pathways in Pseudomonas aeruginosa have gained attention for their potential therapeutic applications, including enhancing the efficacy of existing therapeutic agents against resistant strains. Additionally, these chemical agents can be utilized in various fields such as developing anticancer therapeutics and artificial biological systems.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Kayeen Vadakkan, Ajit Kumar Ngangbam, Kuppusamy Sathishkumar, Nelson Pynadathu Rumjit, Meena Kochappan Cheruvathur
Summary: Pseudomonas aeruginosa, a competitive and biofilm organism with complex quorum systems, poses a significant threat to the medical industry. Inhibiting quorum sensing could be a potential strategy for treating bacterial infections and developing anti-virulent tools.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2024)
Article
Biochemistry & Molecular Biology
Suqi Hao, Dan Yang, Ling Zhao, Fei Shi, Gang Ye, Hualin Fu, Juchun Lin, Hongrui Guo, Ran He, Jianlong Li, Hongwei Chen, Muhammad Faraz Khan, Yinglun Li, Huaqiao Tang
Summary: EGCG, a bioactive ingredient in green tea, demonstrated significant inhibitory effects on the production of virulence factors in Pseudomonas aeruginosa, potentially serving as a candidate for quorum sensing inhibition to combat bacterial infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Infectious Diseases
Ahmed Al Saqr, Mohammed F. Aldawsari, El-Sayed Khafagy, Moataz A. Shaldam, Wael A. H. Hegazy, Hisham A. Abbas
Summary: Pseudomonas aeruginosa can cause healthcare-associated infections through its virulence factors controlled by the quorum sensing system. Allopurinol, an FDA-approved drug, shows promising anti-virulence and anti-QS activities by competing with autoinducers and downregulating QS genes. It may be useful in future treatment of P. aeruginosa infections.
Article
Microbiology
Wen-Ru Li, Tao-Hua Zeng, Zhi-Qing Zhang, Qing-Shan Shi, Xiao-Bao Xie
Summary: In this study, it was found that geraniol can inhibit the growth of Pseudomonas aeruginosa, prolong the lag phase and growth period. Geraniol also suppresses the expression of the three quorum sensing systems of P. aeruginosa, thereby attenuating the virulence factors regulated by these systems. This research is significant for improving the treatment of bacterial infections caused by P. aeruginosa.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Microbiology
Dan Yang, Suqi Hao, Ling Zhao, Fei Shi, Gang Ye, Yuanfeng Zou, Xu Song, Lixia Li, Zhongqiong Yin, Xiaoli He, Shiling Feng, Helin Chen, Yu Zhang, Yuanze Gao, Yinglun Li, Huaqiao Tang
Summary: The study found that paeonol has good anti-biofilm activity against Gram-negative bacteria and anti-QS activity, effectively reducing the virulence of P. aeruginosa. In vivo studies showed that paeonol could reduce the pathogenicity of P. aeruginosa and enhance the survival rate of C. elegans.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Medicine, Research & Experimental
Ya Fei Geng, Cheng Yang, Yi Zhang, Sheng Nan Tao, Jie Mei, Xu Chang Zhang, Ya Juan Sun, Bing Tian Zhao
Summary: This study investigated the potential of luteolin as a quorum sensing inhibitor against Pseudomonas aeruginosa, demonstrating its effectiveness in inhibiting biofilm formation, virulence factor production, and bacterial motility. Luteolin was also found to reduce the accumulation of QS signaling molecules and downregulate the transcription of QS genes, suggesting its promising role in combating drug-resistant infections caused by P. aeruginosa.
Article
Microbiology
Jieying Pu, Shebin Zhang, Xi He, Jianming Zeng, Cong Shen, Yanfen Luo, Honglin Li, Yifei Long, Jianping Liu, Qian Xiao, Yang Lu, Bin Huang, Cha Chen
Summary: A novel QS regulatory sRNA AmiL has been identified in P. aeruginosa, which influences diverse QS-mediated virulence factors and regulates QS gene expression and C4-HSL production.
MICROBIOLOGY SPECTRUM
(2022)
Article
Plant Sciences
Muzamil Ahmad Rather, Kuldeep Gupta, Manabendra Mandal
Summary: The study evaluated the inhibitory effect of methanol extract of Cuphea carthagenensis on biofilm and quorum sensing (QS) activity in Pseudomonas aeruginosa, demonstrating a significant suppression of biofilm formation and virulence factors.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Microbiology
Zhidong Zhang, Yang Sun, Yuanyang Yi, Xiaoyu Bai, Liying Zhu, Jing Zhu, Meiying Gu, Yanlei Zhu, Ling Jiang
Summary: A strain of Streptomyces with quorum-sensing inhibitory activity was isolated from the Kumutag Desert in Xinjiang, and it effectively inhibited biofilm formation and virulence factor production in bacteria such as Pseudomonas aeruginosa.
Article
Microbiology
Priyanikha Jayakumar, Alexandre R. T. Figueiredo, Rolf Kummerli
Summary: Pseudomonas aeruginosa populations undergo extensive genetic adaptation and diversification in various environments. Mutations in the quorum sensing (QS) system affect the expression of virulence factors and public goods. This study found that mutations in different QS systems lead to diverging effects on the QS trait profile, potentially impacting fitness and virulence.
Article
Biotechnology & Applied Microbiology
Wen-Ru Li, Zhi-Qing Zhang, Kang Liao, Qing-Shan Shi, Xu-Bin Huang, Xiao-Bao Xie
Summary: Sulfur compounds found in garlic, such as diallyl trisulfide (DATS), diallyl disulfide (DADS), and diallyl sulfide (DAS), can inhibit the quorum sensing and virulence of Pseudomonas aeruginosa. Among these compounds, DATS exhibits the strongest inhibitory effects. These findings are significant for the control of P. aeruginosa virulence and pathogenicity.
INTERNATIONAL BIODETERIORATION & BIODEGRADATION
(2022)
Article
Biochemistry & Molecular Biology
Megha Shah, Veronique L. Taylor, Diane Bona, Yvonne Tsao, Sabrina Y. Stanley, Sheila M. Pimentel-Elardo, Matthew McCallum, Joseph Bondy-Denomy, P. Lynne Howell, Justin R. Nodwell, Alan R. Davidson, Trevor F. Moraes, Karen L. Maxwell
Summary: The study identified a new phage anti-activator protein, Aqs1, which inhibits phage infection by suppressing the quorum-sensing master regulator LasR. Aqs1 also inhibits the bacterial type IV pilus assembly ATPase protein PilB, preventing phages from superinfecting host cells. This research highlights the potential of small phage proteins to disrupt key biological pathways and offers insights into the evolutionary dynamics between phages and their hosts.
Article
Biochemistry & Molecular Biology
Maan T. T. Khayat, Hisham A. A. Abbas, Tarek S. S. Ibrahim, Samar S. S. Elbaramawi, Ahdab N. N. Khayyat, Majed Alharbi, Wael A. H. Hegazy, Fatma Al-zahraa A. Yehia
Summary: The study evaluated the anti-virulence activities of the vildagliptin-metformin combination against Pseudomonas aeruginosa, showing significant inhibition of biofilm formation and virulence factor production, increased susceptibility to oxidative stress, and relief of inflammation in mice. The combination, targeting quorum sensing systems, downregulated the expression of main QS-encoding genes in P. aeruginosa. These findings highlight the potential of repurposing vildagliptin and metformin as antimicrobial agents.
Article
Microbiology
Michaela J. Eickhoff, Chenyi Fei, Jian-Ping Cong, Bonnie L. Bassler
Summary: Quorum sensing is a chemical communication process in bacteria, and LuxT is a global regulator controlling over 400 genes in V. harveyi through both SwrZ-dependent and SwrZ-independent mechanisms. LuxT is highly conserved among Vibrionaceae, while swrZ is less well conserved.
Article
Biochemistry & Molecular Biology
Todd M. Greco, Christopher Secker, Eduardo Silva Ramos, Joel D. Federspiel, Jeh-Ping Liu, Alma M. Perez, Ismael Al-Ramahi, Jeffrey P. Cantle, Jeffrey B. Carroll, Juan Botas, Scott O. Zeitlin, Erich E. Wanker, Ileana M. Cristea
Summary: Huntington disease is a neurodegenerative disorder with multifactorial pathobiology. This study identifies perturbed protein-protein interactions involving the huntingtin protein, suggesting the influence of cellular factors on disease progression. The findings reveal that these interactions are affected by expanded polyglutamine and are associated with impaired synaptic communication and lysosomal acidification.
Article
Biology
Manutea C. Serrero, Virginie Girault, Sebastian Weigang, Todd M. Greco, Ana Ramos-Nascimento, Fenja Anderson, Antonio Piras, Ana Hickford Martinez, Jonny Hertzog, Anne Binz, Anja Pohlmann, Ute Prank, Jan Rehwinkel, Rudolf Bauerfeind, Ileana M. Cristea, Andreas Pichlmair, Georg Kochs, Beate Sodeik, Adam P. Geballe
Summary: This study identifies an interferon-inducible protein, MxB, that can sense herpesviral capsids and disassemble them, thereby restricting viral nuclear targeting and progeny capsid assembly, leading to enhanced innate immune responses.
Article
Biochemical Research Methods
Michelle A. Kennedy, Todd M. Greco, Bokai Song, Ileana M. Cristea
Summary: Huntington's disease is a progressive neurological disorder caused by polyglutamine expansion of the huntingtin protein. Researchers have developed a web-based platform called HTT-OMNI to visualize and explore potential huntingtin protein interactors and their associated omics measurements.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Biochemistry & Molecular Biology
Isabelle R. Taylor, Philip D. Jeffrey, Dina A. Moustafa, Joanna B. Goldberg, Bonnie L. Bassler
Summary: The opportunistic pathogen Pseudomonas aeruginosa causes antibiotic-resistant, nosocomial infections in immunocompromised individuals and is a high priority for antimicrobial development. Pathogenicity in P. aeruginosa is controlled by the cell-to-cell communication process called quorum sensing (QS), which involves the synthesis, release, and detection of signal molecules. In this study, disruption of the interaction between the QS transcription factor RhlR and the hydrolase PqsE attenuated P. aeruginosa infection in a murine host. The crystallographic analysis revealed that a loop rearrangement induced by the PqsE(E182W) substitution was responsible for the loss of interaction. This study provides insights into the development of drugs targeting PqsE in combating P. aeruginosa infections.
Article
Biochemistry & Molecular Biology
Ameya A. Mashruwala, Boyang Qin, Bonnie L. Bassler
Summary: Bacterial colonies composed of genetically identical individuals can diversify through T6SS-mediated cell death, resulting in variant cells with distinct genotypes. This variant outgrowth is regulated by quorum sensing and T6SS-driven killing, promoting genetic diversity in bacteria.
Article
Microbiology
Jojo A. Prentice, Andrew A. Bridges, Bonnie L. Bassler
Summary: This study investigates how quorum sensing and c-di-GMP signaling jointly regulate biofilm morphogenesis in bacteria, showing a surprising synergy between these two major sensory inputs in controlling biofilm development.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Multidisciplinary Sciences
Boyang Qin, Bonnie L. Bassler
Summary: Bacterial cells at fluid interfaces can self-assemble into soft living materials, called pellicles. Using Vibrio cholerae as a model system, researchers identified matrix proteins and a key quorum-sensing regulator that drive mechanical instabilities underlying pellicle morphogenesis, resulting in fractal patterning. Manipulation of these components could enable precise engineering of biomaterial morphologies.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Justin E. Silpe, Olivia P. Duddy, Bonnie L. Bassler
Summary: This study reveals that bacteriophages can manipulate the bacterial cell-to-cell communication process and trigger the death of host bacteria. The activity of a specific phage receptor is modulated by noncognate signaling molecules and synthetic inhibitors. The findings suggest that the density and species composition of bacterial communities can influence the outcome of bacterial-phage interactions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Dawei Liu, Krystal K. Lum, Nicholas Treen, Corazon T. Nunez, Jinhang Yang, Timothy R. Howard, Michael Levine, Ileana M. Cristea
Summary: IFI16 is an important sensor of nuclear pathogenic DNA that initiates innate immune responses through liquid-liquid phase separation (LLPS) and suppresses viral transcription. Phosphorylation of multiple sites within the intrinsically disordered region (IDR) of IFI16 combinatorially activates LLPS, enabling its filamentation and decoupling of immune signaling from viral transcription repression. These findings demonstrate how IFI16 achieves switch-like phase transitions with temporal resolution and reveal the multi-layered regulation of nuclear DNA sensors.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Microbiology
Chloe McCollum, Allison Didychuk, Dawei Liu, Laura Murray-Nerger, Ileana Cristea, Britt Glaunsinger
Summary: Beta- and gamma-herpesviruses transcribe their late genes differently from host transcription through a complex of viral transcriptional activator proteins. In this study, we identified the catalytic subunit of the viral DNA packaging motor, ORF29, as a component of the Kaposi's sarcoma-associated herpesvirus (KSHV) late gene transcriptional complex, and showed that it enhances late gene expression. Furthermore, we demonstrated that ORF29's catalytic activity is essential for viral transcription and accumulation of crucial late proteins during infection.
Article
Biochemistry & Molecular Biology
Arielle Shkedi, Isabelle R. Taylor, Frank Echtenkamp, Poornima Ramkumar, Mohamed Alshalalfa, Genesis M. Rivera-Marquez, Michael A. Moses, Hao Shao, Robert Jeffrey Karnes, Len Neckers, Felix Feng, Martin Kampmann, Jason E. Gestwicki
Summary: Castration-resistant prostate cancer (CRPC) is associated with increased reliance on heat shock protein 70 (HSP70) and mitochondrial chaperone protein, HSP60, is selectively required in CRPC cell lines. Knockdown of HSP60 results in loss of mitochondrial spare respiratory capacity and poor survival in prostate cancer patients.
CELL CHEMICAL BIOLOGY
(2022)