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Toll/interleukin-1 like receptors are evolutionarily conserved proteins in eukaryotes that play crucial role in pathogen recognition and innate immune responses. Brucella are facultative intracellular bacterial pathogens causing brucellosis in animal and human hosts. Brucella behave as a stealthy pathogen by evading the immune recognition or suppressing the TLR signaling cascades. Brucella encode a TIR domain containing protein, TcpB, which suppresses NF-kappaB activation as well as pro-inflammatory cytokine secretion mediated by TLR2 and TLR4 receptors. TcpB targets the TIRAP mediated pathway to suppress TLR signaling. With the objective of detailed characterization, we have over expressed and purified TcpB from Brucella melitensis in native condition. The purified protein exhibited lipid-binding properties and cell permeability. NF-kappaB inhibition property of endogenous TcpB has also been demonstrated. The data provide insight into the mechanism of action of TcpB in the intracellular niche of Brucella.
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http://dx.doi.org/10.1016/j.bbrc.2010.05.056 | DOI Listing |
Cell Death Differ
September 2025
State Key Laboratory for Managing Biotic and Chemical Treats to the Quality and Safety of Agro-products, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.
The death of fungal cells has been studied in a variety of contexts including responses to antifungal drugs, during fungal developmental processes, in response to bacterial or mycoviral fungal pathogens, and during non-self-recognition between distinct strains of the same species (allorecognition). Some of the genetic determinants and molecular mechanisms of fungal cell death processes are now beginning to be understood in detail. Recent advances have uncovered fungal cell death machinery that shares ancestry with key actors of immune cell death in other eukaryotic and prokaryotic taxa.
View Article and Find Full Text PDFNew Phytol
August 2025
Department of Plant and Environmental Sciences, Weizmann Institute of Science, 7610001, Rehovot, Israel.
Algal blooms and their demise by viruses drive global-scale ecological processes in the ocean. These blooms form the foundation of marine food webs, regulate microbial communities, and shape biogeochemical cycles. Although algal populations are constantly infected by viruses, resistant subpopulations frequently emerge after the infection.
View Article and Find Full Text PDFNat Chem Biol
August 2025
Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
SARM1 is a key executioner of axonal degeneration, acting through NAD⁺ depletion by NADase activity of its TIR domain. Although normally autoinhibited, SARM1 becomes activated in response to axonal damage; however, the underlying mechanism remains unclear. Here, using a class of pyridine-containing compounds that trigger SARM1-dependent axon degeneration, we uncover a two-step activation process.
View Article and Find Full Text PDFJ Peripher Nerv Syst
September 2025
The Jackson Laboratory, Bar Harbor, Maine, USA.
Background: Charcot-Marie-Tooth (CMT) disease can be caused by mutations in over 100 different genes, most of which lead to demyelination (type 1) or degeneration (type 2) of peripheral motor and sensory axons. SARM1 is a protein involved in the active process of Wallerian degeneration after axonal injury. Inhibition of SARM1 protects against axon degeneration following injury or in cases such as chemotherapy-induced peripheral neuropathy.
View Article and Find Full Text PDFJ Inflamm Res
August 2025
Laboratory of Bacterial Pathogenesis, National Institute of Animal Biotechnology, Hyderabad, Telangana, 500032, India.
Introduction: Toll-like receptors (TLRs) are critical components of innate immunity, recognizing microbe-derived molecules and triggering pro-inflammatory cytokine production for pathogen clearance. However, TLR hyperactivation can cause excessive inflammation, contributing to disorders such as sepsis. Thus, modulating TLR signalling is a promising therapeutic strategy.
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