A bioelectrochemical sensing system based on a novel whole-cell redox reactivation/cycling module for ultrasensitive detection of pyocyanin (the biomarker of Pseudomonas aeruginosa infections) was developed. The electroactive bacteria mediated redox reactivation module was constructed using Shewanella oneidensis MR-1 cells as the bioelectro-catalyst and lactate as the electron donor. It could regenerate reductive pyocyanin from its oxidative state, which enabled pyocyanin molecule repeatedly registered by the electrode. Uniquely, with this redox reactivation module, the electrochemical response of pyocyanin was amplified about 405 times (1.3 μA/nM vs. 3.2nA/nM). Thus, an ultrasensitive bioelectrochemical sensing system for pyocyanin quantification was developed by integrating the pyocyanin reactivation module with conventional electrochemical detection system. Remarkably, with this developed biosensing system, an extremely low LOD of 47±1pM was reached. Additionally, this biosensing system showed excellent resistance to interferences from human fluids or bacterial contamination. This work provided a simple, ultrasensitive and robust tool for pyocyanin detection, and more importantly, demonstrated a new dimension for electrochemical signal amplification in biosensing.
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http://dx.doi.org/10.1016/j.bios.2017.07.008 | DOI Listing |
Cell Death Dis
December 2024
Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt, Germany.
The concept of Targeted Protein Degradation (TPD) has been introduced as an attractive alternative to the development of classical inhibitors. TPD can extend the range of proteins that can be pharmacologically targeted beyond the classical targets for small molecule inhibitors, as a binding pocket is required but its occupancy does not need to lead to inhibition. The method is based on either small molecules that simultaneously bind to a protein of interest and to a cellular E3 ligase and bring them in close proximity (molecular glue) or a bi-functional molecule synthesized from the chemical linkage of a target protein-specific small molecule and one that binds to an E3 ligase (Proteolysis Targeting Chimeras (PROTAC)).
View Article and Find Full Text PDFCell Host Microbe
December 2024
Department of Microbiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address:
Most bacteria are polylysogens that carry multiple prophages integrated into the chromosome. These prophages confer advantages to their bacterial host, yet also pose a lethal threat as they can reactivate and enter a lytic cycle. DNA damage of the bacterial host is a common trigger of prophage lytic cycles.
View Article and Find Full Text PDFVirus Res
December 2024
Oklahoma State University, College of Veterinary Medicine, Department of Veterinary Pathobiology, Stillwater, OK 74078, USA. Electronic address:
Glucocorticoid receptor (GR) activation enhances Human alpha-herpes virus 1 (HSV-1) replication and explant-induced reactivation from latency. Furthermore, GR and Krüppel-like factor 15 (KLF15) cooperatively transactivate cis-regulatory modules (CRMs) that drive expression of infected cell protein 0 (ICP0), ICP4, and ICP27. KLF and specificity protein (Sp) family members bind GC-rich or C-rich sequences and belong to the same super-family of transcription factors.
View Article and Find Full Text PDFbioRxiv
September 2024
Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
The latent HIV reservoir is a major barrier to HIV cure. Combining latency reversal agents (LRAs) with differing mechanisms of action such as AZD5582, a non-canonical NF-kB activator, and I-BET151, a bromodomain inhibitor is appealing towards inducing HIV-1 reactivation. However, even this LRA combination needs improvement as it is inefficient at activating proviruses in cells from people living with HIV (PLWH).
View Article and Find Full Text PDFCancer Discov
December 2024
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
The Hippo signaling pathway is commonly dysregulated in human cancer, which leads to a powerful tumor dependency on the YAP/TAZ transcriptional coactivators. In this study, we used paralog cotargeting CRISPR screens to identify kinases MARK2/3 as absolute catalytic requirements for YAP/TAZ function in diverse carcinoma and sarcoma contexts. Underlying this observation is the direct MARK2/3-dependent phosphorylation of NF2 and YAP/TAZ, which effectively reverses the tumor suppressive activity of the Hippo module kinases LATS1/2.
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