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- Varicella‑Zoster Virus ORF39 Transmembrane Protein Suppresses Interferon‑Beta Promoter Activation by Interacting with STING
- Gwang Myeong Lee , Shuang Gong , Seong&# , Hyemin Ko , Woo&# , Jihyun Lee , Ok Sarah Shin , Jin&#
- J. Microbiol. 2023;61(2):259-270. Published online February 20, 2023
- DOI: https://doi.org/10.1007/s12275-023-00019-7
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Abstract
- Varicella-Zoster virus (VZV) causes varicella in primary infection of children and zoster during reactivation in adults. Type I interferon (IFN) signaling suppresses VZV growth, and stimulator of interferon genes (STING) plays an important role in anti-VZV responses by regulating type I IFN signaling. VZV-encoded proteins are shown to inhibit STING-mediated activation of the IFN-β promoter. However, the mechanisms by which VZV regulates STING-mediated signaling pathways are largely unknown. In this study, we demonstrate that the transmembrane protein encoded by VZV open reading frame (ORF) 39 suppresses STING-mediated IFN-β production by interacting with STING. In IFN-β promoter reporter assays, ORF39 protein (ORF39p) inhibited STING-mediated activation of the IFN-β promoter. ORF39p interacted with STING in co-transfection assays, and this interaction was comparable to that of STING dimerization. The cytoplasmic N-terminal 73 amino acids region of ORF39P was not necessary for ORF39 binding and suppression of STING-mediated IFN-β activation. ORF39p also formed a complex containing both STING and TBK1. A recombinant VZV expressing HA-tagged ORF39 was produced using bacmid mutagenesis and showed similar growth to its parent virus. During HA-ORF39 virus infection, the expression level of STING was markedly reduced, and HA-ORF39 interacted with STING. Moreover, HA-ORF39 also colocalized with glycoprotein K (encoded by ORF5) and STING at the Golgi during virus infection. Our results demonstrate that the transmembrane protein ORF39p of VZV plays a role in evading the type I IFN responses by suppressing STINGmediated activation of the IFN-β promoter.
- Biophysical characterization of antibacterial compounds derived from pathogenic fungi Ganoderma boninense
- Syahriel Abdullah , Yoon Sin Oh , Min-Kyu Kwak , KhimPhin Chong
- J. Microbiol. 2021;59(2):164-174. Published online December 23, 2020
- DOI: https://doi.org/10.1007/s12275-021-0551-8
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- 8 Citations
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Abstract
- There have been relatively few studies which support a link
between Ganoderma boninense, a phytopathogenic fungus
that is particularly cytotoxic and pathogenic to plant tissues
and roots, and antimicrobial compounds. We previously observed
that liquid-liquid extraction (LLE) using chloroformmethanol-
water at a ratio (1:1:1) was superior at detecting
antibacterial activities and significant quantities of antibacterial
compounds. Herein, we demonstrate that antibacterial
secondary metabolites are produced from G. boninense mycelia.
Antibacterial compounds were monitored in concurrent
biochemical and biophysical experiments. The combined
methods
included high performance thin-layer chromatography (HPTLC), gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), fourier transform infrared (FTIR), and nuclear magnetic resonance (NMR) spectroscopy. The antibacterial compounds derived from mycelia with chloroform-methanol extraction through LLE were isolated via a gradient solvent elution system using HPTLC. The antibacterial activity of the isolated compounds was observed to be the most potent against Staphylococcus aureus ATCC 25923 and multidrug-resistant S. aureus NCTC 11939. GC-MS, HPLC, and FTIR analysis confirmed two antibacterial compounds, which were identified as 4,4,14α-trimethylcholestane (m/z = 414.75; lanostane, C30H54) and ergosta-5,7,22-trien-3β-ol (m/z = 396.65; ergosterol, C28H44O). With the aid of spectroscopic evaluations, ganoboninketal (m/z = 498.66, C30H42O6), which belongs to the 3,4-seco-27-norlanostane triterpene family, was additionally characterized by 2D-NMR analysis. Despite the lack of antibacterial potential exhibited by lanostane; both ergosterol and ganoboninketal displayed significant antibacterial activities against bacterial pathogens. Results provide evidence for the existence of bioactive compounds in the mycelia of the relatively unexplored phytopathogenic G. boninense, together with a robust method for estimating the corresponding potent antibacterial secondary metabolites.
Review
- Recent advances in the development of β-lactamase inhibitors
- Shivakumar S. Jalde , Hyun Kyung Choi
- J. Microbiol. 2020;58(8):633-647. Published online July 27, 2020
- DOI: https://doi.org/10.1007/s12275-020-0285-z
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- 20 Citations
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Abstract
- β-Lactam antibiotics are the most commonly prescribed antibiotics worldwide; however, antimicrobial resistance (AMR) is a global challenge. The β-lactam resistance in Gram-negative bacteria is due to the production of β-lactamases, including extended-spectrum β-lactamases, metallo-β-lactamases, and carbapenem-hydrolyzing class D β-lactamases. To restore the efficacy of BLAs, the most successful strategy is to use them in combination with β-lactamase inhibitors (BLI). Here we review the medically relevant β-lactamase families and penicillins, diazabicyclooctanes, boronic acids, and novel chemical scaffold-based BLIs, in particular approved and under clinical development.
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