Biology subjects

Yoo, J.-S.

Publications and source records attributed to Yoo, J.-S..

6 recordsLinked to original sources

bioRxiv2025

Kinetic Plasticity of Nitrite-Oxidizing Bacteria Containing Cytoplasmic Nitrite Oxidoreductase

Nitrite oxidation, the second step of nitrification, is essential to the global nitrogen cycle. Nitrite-oxidizing bacteria (NOB) are classified into two groups based on the cellular localization of their key enzyme nitrite oxidoreductase (NXR): periplasmic (pNXR) and cytoplasmic (cNXR). The use of a cNXR by NOB has been reported to be linked to a lower nitrite affinity and energy efficiency of nitrite oxidation, indicating adaptation to nitrogen-rich environments. In this study, cNXR NOB model strains demonstrated nitrite concentration-dependent shifts in optimal growth pH, a behavior not observed in pNXR NOB. Nitrobacter winogradskyi Nb-255 (cNXR NOB), grown at 1 mM nitrite (pH 7.5), exhibited a high nitrite affinity in terms of apparent Km (25.9 M) and a high specific affinity a{degrees} (440.5 l g cells-1 h-1), both comparable to pNXR NOB in microrespirometry-based kinetic assays. Unexpectedly, cells pre-grown at 10 mM nitrite (pH 7.5) achieved a pNXR-like affinity at pH 5.5 without prior adaptation to acidic conditions. In contrast, pNXR NOB exhibited consistent kinetic behavior across different pH conditions. Kinetic inhibition in the presence of nitrate suggested that this plasticity is driven by a regulated interplay between nitrite uniport and nitrite/nitrate antiporter systems. Our findings indicate that Nitrobacter can dynamically modulate nitrite affinity in response to both nitrite concentration and pH, conferring a flexible adaptation strategy that features traits of both r-and K-strategists across a range of environmental conditions. This adaptive plasticity likely extends to other cNXR-containing NOB in response to fluctuating environmental conditions.

microbiology↗

bioRxiv2025

Bacterial glycosphingolipids orchestrate colonization and immune modulation in neonatal host

Symbiotic microbiota has co-existed with the mammalian host over millennia, conserving a stable community structure generation after generation. During the vertical transmission, gut symbionts rapidly colonize the unoccupied host lumen, nonetheless, how symbionts adapt to the dynamic changes of host environment, and contribute to the structural and immunological maturation remains elusive. Here, we show that the early gut symbiont Bacteroides fragilis produces a species- and stage-specific sphingolipid, alpha-galactosylceramide (BfaGC), that orchestrates neonatal colonization and immune modulation. BfaGC stabilizes membrane integrity and facilitates aerobic respiration, providing a critical advantage under early-life oxygen exposure. Temporally induced in the neonatal gut, BfaGC is necessary to regulate colonic type I natural killer T (NKT) cells, highlighting metabolic adaptation of the symbiont is synchronized with the time-sensitive host development. These findings reveal a mutualistic benefit exerted by endobiotic lipid metabolites in host-microbe interactions and provide new insights into species-specific mechanisms in early microbiota establishment and host immune education.

microbiology↗

bioRxiv2025

Identification of novel cis-acting elements, E-box and ISRE, regulating IFNγ-IRF1 axis-mediated NLRC5 expression

NLRC5 and CIITA are the primary transcriptional regulators of MHC class I and MHC class II, respectively, and play essential roles in adaptive immunity. While the regulatory mechanisms of CIITA have been extensively characterized, the transcriptional control of NLRC5 remains incompletely understood. In this study, we identified two novel conserved cis-regulatory elements within the NLRC5 promoter, an E-box and an ISRE. Furthermore, we revealed IRF1 as a novel transcriptional regulator of NLRC5, binding directly to the ISRE within the NLRC5 promoter. Using the newly identified NLRC5 ISRE, we established a screening platform to identify modulators of the IFN{gamma}-IRF1-NLRC5 axis. This system corroborated the inhibitory effects of known viral antagonists and led to the identification of novel SARS-CoV-2 viral factors that suppress IFN{gamma}- mediated IRF1 nuclear translocation, thereby inhibiting the MHC class I pathway. By elucidating the previously unproven molecular mechanism underlying IFN{gamma}-mediated NLRC5 regulation, our study provides critical insights into viral immune evasion strategies and the modulation of antigen presentation. These findings may facilitate the development of MHC class I-targeted therapeutics by modulating the IRF1-NLRC5 axis.

immunology↗

bioRxiv2025

DNA topological regulation by topoisomerase IIbeta-DNA-PK interaction is important for controlled hypoxia-inducible gene expression

Hypoxic stress responses are essential for cellular and organismal survival and drive gene regulation across diverse biological pathways, including cell cycle progression and energy metabolism. Here, we show that topoisomerase II{beta} (TOP2B) regulates DNA topology and transcription of hypoxia-inducible genes (HIGs) in a DNA-dependent protein kinase (DNA-PK)-dependent manner. Integrated cellular, biochemical, and genomic analyses reveal an antagonistic yet correlated relationship between TOP2B and DNA-PK activities. Under normoxic conditions, TOP2B associates with HIGs and represses transcription by suppressing DNA negative supercoiling formation and accessibility. Under hypoxic exposure, TOP2B dissociates from HIGs, while DNA-PK and HIF1 are recruited to activate HIGs. Notably, DNA-PK is required for the repressive function of TOP2B, as DNA-PK knockout abrogates TOP2B release and activity, resulting in elevated expression of a number of HIGs. Mechanistically, DNA-PK phosphorylates TOP2B at T1403, stimulating its catalytic activity to restrain DNA unwinding and accessibility, thereby suppressing HIG transcription. Collectively, these findings identify a novel role for TOP2B and DNA-PK-mediated regulation of TOP2B as key transcriptional regulators of HIG expression. We propose that phosphorylation-dependent modulation of TOP2B activity is coordinated with transcriptional states and determines DNA topology to regulate Pol II transcription.

molecular biology↗

bioRxiv2023

Functional and metagenomic level diversities of human gut symbiont-derived glycolipids

Bioactive metabolites produced by symbiotic microbiota causally impact host health and disease, nonetheless, incomplete functional annotation of genes as well as complexities and dynamic nature of microbiota make understanding species-level contribution in production and actions difficult. Alpha-galactosylceramides produced by Bacteroides fragilis (BfaGC) are one of the first modulators of colonic immune development, but biosynthetic pathways and the significance of the single species in the symbiont community still remained elusive. To address these questions at the microbiota level, we have investigated the lipidomic profiles of prominent gut symbionts and the metagenome-level landscape of responsible gene signatures in the human gut. We first elucidated the chemical diversity of sphingolipid biosynthesis pathways of major bacterial species. In addition to commonly shared ceramide backbone synthases showing two distinct intermediates, alpha-galactosyltransferase (agcT), the necessary and sufficient component for BfaGC production and host colonic type I natural killer T (NKT) cell regulation by B. fragilis, was characterized by forward-genetics based targeted metabolomic screenings. Phylogenetic analysis of agcT in human gut symbionts revealed that only a few ceramide producers have agcT and hence can produce aGCs, on the other hand, structurally conserved homologues of agcT are widely distributed among species lacking ceramides. Among them, alpha-glucosyl-diacylglycerol(aGlcDAG)-producing glycosyltransferases with conserved GT4-GT1 domains are one of the most prominent homologs in gut microbiota, represented by Enterococcus bgsB. Of interest, aGlcDAGs produced by bgsB can antagonize BfaGC-mediated activation of NKT cells, showing the opposite, lipid structure-specific actions to regulate host immune responses. Further metagenomic analysis of multiple human cohorts uncovered that the agcT gene signature is almost exclusively contributed by B. fragilis, regardless of age, geographical and health status, where the bgsB signature is contributed by >100 species, of which abundance of individual microbes is highly variable. Our results collectively showcase the diversities of gut microbiota producing biologically relevant metabolites in multiple layers-biosynthetic pathways, host immunomodulatory functions and microbiome-level landscapes in the host.

microbiology↗

bioRxiv2022

SARS-CoV-2 variants show temperature-dependent enhancedpolymerase activity in the upper respiratory tract and high transmissibility

With the convergent global emergence of SARS-CoV-2 variants of concern (VOC), a precise comparison study of viral fitness and transmission characteristics is necessary for the prediction of dominant VOCs and the development of suitable countermeasures. While airway temperature plays important roles in the fitness and transmissibility of respiratory tract viruses, it has not been well studied with SARS-CoV-2. Here we demonstrate that natural temperature differences between the upper (33{degrees}C) and lower (37{degrees}C) respiratory tract have profound effects on SARS-CoV-2 replication and transmission. Specifically, SARS-COV-2 variants containing the P323L or P323L/G671S mutation in the NSP12 RNA-dependent RNA polymerase (RdRp) exhibited enhanced RdRp enzymatic activity at 33{degrees}C compared to 37{degrees}C and high transmissibility in ferrets. MicroScale Thermophoresis demonstrated that the NSP12 P323L or P323L/G671S mutation stabilized the NSP12-NSP7-NSP8 complex interaction. Furthermore, reverse genetics-derived SARS-CoV-2 variants containing the NSP12 P323L or P323L/G671S mutation displayed enhanced replication at 33{degrees}C, and high transmission in ferrets. This suggests that the evolutionarily forced NSP12 P323L and P323L/G671S mutations of recent SARS-CoV-2 VOC strains are associated with increases of the RdRp complex stability and enzymatic activity, promoting the high transmissibility.

microbiology↗