Korea Research Institute of Bioscience and Biotechnology
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Anaerococcus faecalis sp. nov., isolated from swine faeces
No full textAn obligate anaerobic, Gram-stain-positive, non-spore forming, non-motile, catalase and oxidase-negative, coccoid-shaped bacterium designated AGMB00486T was isolated from swine faeces. The optimal growth of the isolate occurred at pH 8.0 and 37 ℃. Furthermore, the growth was observed in the presence of up to 4% (w/v) NaCl but not at salinity levels higher than 5%. The phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain AGMB00486T was a member of the genus Anaerococcus and that the isolate was most closely related to Anaerococcus vaginalis KCTC 15028T (96.7% 16S rRNA gene sequence similarity) followed by Anaerococcus hydrogenalis KCTC 15014T (96.7%) and Anaerococcus senegalensis KCTC 15435T (96.3%). Whole-genome sequence analysis determined that the DNA G+C content of strain AGMB00486T was 30.1 mol%, and the genome size, numbers of tRNA and rRNA genes were 2,268,866 bp, 47 and 8, respectively. The average nucleotide identity values between strain AGMB00486T and the three related type strains were 77.0, 77.4 and 77.2%, respectively. The major cellular fatty acids (> 10%) of strain AGMB00486T were C14:0, C16:0 and C16:0 DMA. Accordingly, these distinct phenotypic and phylogenetic properties revealed that strain AGMB00486T represents a novel species, for which the name Anaerococcus faecalis sp. nov. is proposed. The type strain is AGMB00486T (= KCTC 15945T = CCTCC AB 202009T).
A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein
No full textVaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.
Development of synthetic biology-based microbot for non-invasive diagnosis of ulcerative colitis
No full text궤양성 대장염의 비침습적 진단을 위한 합성생물학 기반 미생물로봇 개발KFM060191
Seasonal succession of microbes in different size-fractions and their modular structures determined by both macro- and micro-environmental filtering in dynamic coastal waters
No full textMicrobes interact with each other in response to various environmental changes in coastal marine ecosystems. To explore how the macroenvironment (environmental filtering) and species-engineered microenvironment (niche construction) affect the ecological network of the marine microbiome in the highly dynamic coastal waters of Korea, we analyzed the modular structures of the microbial community and identified microbial interconnections in different size fractions for a year. Fluctuations in the macroenvironment, such as temperature and nutrient concentrations driven by seasonal changes, are the major factors in determining successive microbial modules. Compared to particle-associated (PA) microbes, free-living (FL) microbes seemed to be more affected by macroenvironmental filtering. Modules related to nutrients were further divided into various modules according to different lifestyles. In addition, a large transient discharge of the Changjiang (Yangtze River) in summer also formed a distinct microbial module, which was related to the high ammonia concentration arising from phytoplankton degradation. Microbes belonging to the SAR11, SAR86, and SAR116 clades, Flavobacteriaceae, and MG IIa-L showed repeated interconnections in temperature-related modules, while the SAR202 clade, Marinimicrobia, DEV007 clade, and Arctic97B-4 and Sva0996 marine groups displayed repeated connections in nutrient-related modules. These ‘skeleton’-forming microbes created species-engineered microenvironments, further fine-tuning microbial modular structures. Furthermore, they serve as keystone species for module stability by linking interdependent microbial partners within their own modules through universally beneficial metabolic activities. Therefore, they could reinforce the ecological resilience of microbial communities under abiotic and biotic perturbations in dynamic coastal waters. In conclusion, both macro- and micro-environmental filtering were important for determining the seasonal succession of microbial community structures.
ZIP8 exacerbates collagen-induced arthritis by increasing pathogenic T cell responses
No full textZinc is a trace element that is essential for immune responses. Therefore, changes in cellular zinc levels in specific immune cells may influence inflammatory autoimmune diseases, such as rheumatoid arthritis (RA). However, the regulation of zinc mobilization in immune cells and its role in the pathogenesis of RA are not fully understood. Thus, we investigated the roles of zinc transporters in RA pathogenesis. We demonstrated that ZIP8 was specifically upregulated in CD4+ T cells that infiltrated the inflamed joint and that ZIP8 deficiency in CD4+ T cells abrogated collagen-induced arthritis. ZIP8 deficiency dramatically affected zinc influx in effector T cells and profoundly reduced T cell receptor (TCR)-mediated signaling, including NF-κB and MAPK signaling, which are pathways that are involved in T helper (Th) 17 cell differentiation. Taken together, our findings suggest that ZIP8 depletion in CD4+ T cells attenuates TCR signaling due to insufficient cellular zinc, thereby reducing the function of effector CD4+ T cells, including Th17 cells. Our results also suggest that targeting ZIP8 may be a useful strategy to inhibit RA development and pathogenesis.
Peroxiredoxin II with dermal mesenchymal stem cells accelerates wound healing
No full textPeroxiredoxin II (Prx II) is involved in proliferation, differentiation, and aging in various cell types. However, Prx II-mediated stem cell regulation is poorly understood. Here, dermal mesenchymal stem cells (DMSCs), cell-growth factor-rich conditioned medium from DMSCs (DMSC-CM), and DMSC-derived exosomes (DMSC-Exos) were used to explore the regulatory role of Prx II in DMSC wound healing. Following treatment, wound healing was significantly decelerated in Prx II-/- DMSCs than in Prx II+/+ DMSCs. In vitro stimulation with 10 μM H2O2 significantly increased apoptosis in Prx II-/- DMSCs compared with Prx II+/+ DMSCs. The mRNA expression levels of EGF, b-FGF, PDGF-B, and VEGF did not significantly differ between Prx II-/- and Prx II+/+ DMSCs. Fibroblasts proliferated comparably when treated with Prx II+/+ DMSC-CM or Prx II-/- DMSC-CM. Wound healing was significantly higher in the Prx II-/- DMSC-Exos-treated group than in the Prx II+/+ DMSCs-Exos-treated group. Moreover, microRNA (miR)-21-5p expression levels were lower and miR-221 levels were higher in Prx II-/- DMSCs than in Prx II+/+ DMSCs. Therefore, our results indicate that Prx II accelerated wound healing by protecting DMSCs from reactive oxygen species-induced apoptosis; however, Prx II did not regulate cell/growth factor secretion. Prx II potentially regulates exosome functions via miR-21-5p and miR-221.
Fibrinogen-like protein 1 modulates sorafenib resistance in human hepatocellular carcinoma cells
No full textDespite liver cancer being the second-leading cause of cancer-related death worldwide, few systemic drugs have been approved. Sorafenib, the first FDA-approved systemic drug for unresectable hepatocellular carcinoma (HCC), is limited by resistance. However, the precise mechanisms underlying this phenomenon are unknown. Since fibrinogen-like 1 (FGL1) is involved in HCC progression and upregulated after anticancer therapy, we investigated its role in regulating sorafenib resistance in HCC. FGL1 expression was assessed in six HCC cell lines (HepG2, Huh7, Hep3B, SNU387, SNU449, and SNU475) using western blotting. Correlations between FGL1 expression and sorafenib resistance were examined by cell viability, colony formation, and flow cytometry assays. FGL1 was knocked-down to confirm its effects on sorafenib resistance. FGL1 expression was higher in HepG2, Huh7, and Hep3B cells than in SNU387, SNU449, and SNU475 cells; high FGL1-expressing HCC cells showed a lower IC50 and higher sensitivity to sorafenib. In Huh7 and Hep3B cells, FGL1 knockdown significantly increased colony formation by 61% (p = 0.0013) and 99% (p = 0.0002), respectively, compared to that in controls and abolished sorafenib-induced suppression of colony formation, possibly by modulating ERK and autophagy signals. Our findings demonstrate that sorafenib resistance mediated by FGL1 in HCC cells, suggesting FGL1 as a potential sorafenib-resistance biomarker and target for HCC therapy.
Licochalcone A inhibits hypoxia-inducible factor-1α accumulation by suppressing mitochondrial respiration in hypoxic cancer cells
No full textHypoxia-inducible factor (HIF)-1 is an important regulator of the cellular response in the hypoxic tumor environment. While searching for HIF inhibitors derived from natural products that act as anticancer agents, we found that Glycyrrhiza uralensis exerts HIF-1 inhibitory activity in hypoxic cancer cells. Among the five components of G. uralensis, licochalcone A was found to potently suppress hypoxia-induced HIF-1α accumulation and expression of HIF-1α target genes, including GLUT1 and PDK1 in HCT116 cells. Licochalcone A also enhances intracellular oxygen content by directly inhibiting mitochondrial respiration, resulting in oxygen-dependent HIF-1α degradation. Hence, licochalcone A may effectively inhibit ATP production, primarily by reducing the mitochondrial respiration-mediated ATP production rate rather than the glycolysis-mediated ATP production rate. This effect subsequently suppresses cancer cell viability, including that of HCT116, H1299, and H322 cells. Consequently, these results suggest that licochalcone A has therapeutic potential in hypoxic cancer cells.
Transforming growth factor β inhibits MUC5AC expression by Smad3/HDAC2 complex formation and NF-κB deacetylation at K310 in NCI-H292 cells
No full textAirway mucus secretion is an essential innate immune response for host protection. However, overproduction and hypersecretion of mucus, mainly composed of the gel- forming MUC5AC protein, are significant risk factors for patients with asthma and chronic obstructive pulmonary disease (COPD). The transforming growth factor β (TGFβ) signaling pathway negatively regulates MUC5AC expression; however, the underlying molecular mechanism is not fully understood. Here, we showed that TGFβ significantly reduces the expression of MUC5AC mRNA and its protein in NCI-H292 cells, a human mucoepidermoid carcinoma cell line. This reduced MUC5AC expression was restored by a TGFβ receptor inhibitor (SB431542), but not by the inhibition of NF-κB (BAY11-7082 or Triptolide) or PI3K (LY294002) activities. TGFβ-activated Smad3 dose-dependently bound to MUC5AC promoter. Notably, TGFβ-activated Smad3 recruited HDAC2 and facilitated nuclear translocation of HDAC2, thereby inducing the deacetylation of NF-κB at K310, which is essential for a reduction in NF-κB transcriptional activity. Both TGFβ-induced nuclear translocation of Smad3/HDAC2 and deacetylation of NF-κB at K310 were suppressed by a Smad3 inhibitor (SIS3). These results suggest that the TGFβ-activated Smad3/HDAC2 complex is an essential negative regulator for MUC5AC expression and an epigenetic regulator for NF-κB acetylation. Therefore, these results collectively suggest that modulation of the TGFβ1/Smad3/HDAC2/NF-κB pathway axis can be a promising way to improve lung function as a treatment strategy for asthma and COPD.
The metabolite profile in culture supernatant of Aster yomena callus and its anti-photoaging effect in skin cells exposed to UVB
No full textAster yomena (A. yomena) extract has anti-inflammatory, antioxidant, anti-asthma, and anti-atopic effects. However, the commercial use of A. yomena extract requires a long processing time with specific processing steps (including heat treatment and ethanol precipitation), and there are various environmental problems. We aimed to build a system to produce A. yomena extract by culturing the callus in a bioreactor that can allow rapid process scale-up to test the effect of extract (AYC-CS-E) isolated from culture supernatant of A. yomena callus on photoaging of human keratinocytes (HaCaT) caused by ultraviolet B (UVB) exposure. Through screening analysis based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), 17 major metabolites were tentatively identified from AYC-CS-E for the first time. The suppression of cell proliferation caused by UVB was effectively alleviated in UVB-irradiated HaCaT cells treated with AYC-CS-E. Treatment with AYC-CS-E strongly induced the formation of type I procollagen and the inhibition of elastase in UVB-irradiated HaCaT cells and significantly reduced the expression of matrix metalloproteinase (MMP)-1. In addition, treatment of UVB-irradiated HaCaT cells with AYC-CS-E effectively improved various factors associated with an inflammatory reaction, skin damage recovery, skin moisture retention, and hyper-keratinization caused by photoaging, such as reactive oxygen species (ROS), pro-inflammatory cytokines, transforming growth factor beta (TGF-β), MMP-3, MMP-9, filaggrin, hyaluronic acid synthase 2 (HAS-2), keratin 1 (KRT-1), nuclear factor-kappa B (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2) at the gene and protein levels. These results suggest that AYC-CS-E can be used as a cosmetic ingredient for various skin diseases caused by photoaging, and the current callus culture system can be used commercially to supply cosmetic ingredients.