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Frontiers in Oral Health 2024, a member of the "red complex" bacteria implicated in severe periodontitis, employs various survival strategies and virulence factors to interact with the host. It...
, a member of the "red complex" bacteria implicated in severe periodontitis, employs various survival strategies and virulence factors to interact with the host. It thrives as a late colonizer in the oral biofilm, relying on its unique adaptation mechanisms for persistence. Essential to its survival are the type 9 protein secretion system and -glycosylation of proteins, crucial for host interaction and immune evasion. Virulence factors of , including sialidase and proteases, facilitate its pathogenicity by degrading host glycoproteins and proteins, respectively. Moreover, cell surface glycoproteins like the S-layer and BspA modulate host responses and bacterial adherence, influencing colonization and tissue invasion. Outer membrane vesicles and lipopolysaccharides further induce inflammatory responses, contributing to periodontal tissue destruction. Interactions with specific host cell types, including epithelial cells, polymorphonuclear leukocytes macrophages, and mesenchymal stromal cells, highlight the multifaceted nature of pathogenicity. Notably, it can invade epithelial cells and impair PMN function, promoting dysregulated inflammation and bacterial survival. Comparative studies with periodontitis-associated reveal differences in protease activity and immune modulation, suggesting distinct roles in disease progression. potential to influence oral antimicrobial defense through protease-mediated degradation and interactions with other bacteria underscores its significance in periodontal disease pathogenesis. However, understanding precise role in host-microbiome interactions and its classification as a keystone pathogen requires further investigation. Challenges in translating research data stem from the complexity of the oral microbiome and biofilm dynamics, necessitating comprehensive studies to elucidate its clinical relevance and therapeutic implications in periodontitis management.
PubMed: 38872984
DOI: 10.3389/froh.2024.1434217 -
Frontiers in Veterinary Science 2024-glycosylation is a highly conserved glycan modification that plays crucial roles in various physiological processes, including protein folding, trafficking, and signal...
-glycosylation is a highly conserved glycan modification that plays crucial roles in various physiological processes, including protein folding, trafficking, and signal transduction. Porcine deltacoronavirus (PDCoV) poses a newly emerging threat to the global porcine industry. The spike protein of PDCoV exhibits a high level of -glycosylation; however, its role in viral infection remains poorly understood. In this study, we applied a lentivirus-based entry reporter system to investigate the role of -glycosylation on the viral spike protein during PDCoV entry stage. Our findings demonstrate that -glycosylation at positions 652 and 661 of the viral spike protein significantly reduces the infectivity of PDCoV pseudotyped virus. Overall, our results unveil a novel function of -glycosylation in PDCoV infection, highlighting its potential for facilitating the development of antiviral strategies.
PubMed: 38872801
DOI: 10.3389/fvets.2024.1430113 -
Cell Jun 2024
PubMed: 38870945
DOI: 10.1016/j.cell.2024.06.004 -
Synthetic and Systems Biotechnology Dec 2024Digitoxose, a significant 2,6-dideoxyhexose found in nature, exists in many small-molecule natural products. These digitoxose-containing natural products can be divided... (Review)
Review
Digitoxose, a significant 2,6-dideoxyhexose found in nature, exists in many small-molecule natural products. These digitoxose-containing natural products can be divided into steroids, macrolides, macrolactams, anthracyclines, quinones, enediynes, acyclic polyene, indoles and oligosaccharides, that exhibit antibacterial, anti-viral, antiarrhythmic, and antitumor activities respectively. As most of digitoxose-containing natural products for clinical application or preclinical tests, this review also summarizes the biosynthesis of digitoxose, and application of compound diversification by introducing sugar plasmids. It may provide a practical approach to expanding the diversity of digitoxose-containing products.
PubMed: 38868608
DOI: 10.1016/j.synbio.2024.05.012 -
AMB Express Jun 2024High throughput screening (HTS) methods of enzyme variants are essential for the development of robust biocatalysts suited for low impact, industrial scale, biobased...
High throughput screening (HTS) methods of enzyme variants are essential for the development of robust biocatalysts suited for low impact, industrial scale, biobased synthesis of a myriad of compounds. However, for the majority of enzyme classes, current screening methods have limited throughput, or need expensive substrates in combination with sophisticated setups. Here, we present a straightforward, high throughput selection system that couples sucrose synthase activity to growth. Enabling high throughput screening of this enzyme class holds the potential to facilitate the creation of robust variants, which in turn can significantly impact the future of cost effective industrial glycosylation.
PubMed: 38865019
DOI: 10.1186/s13568-024-01727-y -
ELife Jun 2024Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in...
Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work, we show through over 45 μs of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated by -glycosylation at N343 and how this glycan's structural role changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2), and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of the -glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha, and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.
Topics: Glycosylation; Spike Glycoprotein, Coronavirus; SARS-CoV-2; Humans; Molecular Dynamics Simulation; Protein Binding; COVID-19; Polysaccharides; Protein Domains; Binding Sites; Protein Conformation; Mutation
PubMed: 38864493
DOI: 10.7554/eLife.95708 -
Horticulture Research Jun 2024Citrus fruits have abundant flavonoid glycosides (FGs), an important class of natural functional and flavor components. However, there have been few reports about the...
Citrus fruits have abundant flavonoid glycosides (FGs), an important class of natural functional and flavor components. However, there have been few reports about the modification of UDP-glycosyltransferases (UGTs) on flavonoids in citrus. Notably, in flavonoid biosynthesis, 7--glucosylation is the initial and essential step of glycosylation prior to the synthesis of flavanone disaccharides, the most abundant and iconic FGs in citrus fruits. Here, based on the accumulation of FGs observed at the very early fruit development stage of two pummelo varieties, we screened six novel flavonoid 7--glucosyltransferase genes () transcriptomic analysis and then characterized them . The results revealed that four Cg7GlcTs possess wide catalytic activities towards various flavonoid substrates, with CgUGT89AK1 exhibiting the highest catalytic efficiency. Transient overexpression of and led to increases in FG synthesis in pummelo leaves. Interestingly, these two genes had conserved sequences and consistent functions across different germplasms. Moreover, was found to play a role in the response of citrus to Huanglongbing infection by promoting FG production. The findings improve our understanding of flavonoid 7--glucosylation by identifying the key genes, and may help improve the benefits of flavonoid biosynthesis for plants and humans in the future.
PubMed: 38863995
DOI: 10.1093/hr/uhae098 -
Biology Letters Jun 2024Glycation reactions play a key role in the senescence process and are involved in numerous age-related pathologies, such as diabetes complications or Alzheimer's... (Review)
Review
Glycation reactions play a key role in the senescence process and are involved in numerous age-related pathologies, such as diabetes complications or Alzheimer's disease. As a result, past studies on glycation have mostly focused on human and laboratory animal models for medical purposes. Very little is known about glycation and its link to senescence in wild animal species. Yet, despite feeding on high-sugar diets, several bat and bird species are long-lived and seem to escape the toxic effects of high glycaemia. The study of these models could open new avenues both for understanding the mechanisms that coevolved with glycation resistance and for treating the damaging effects of glycations in humans. Our understanding of glycaemia's correlation to proxies of animals' pace of life is emerging in few wild species; however, virtually nothing is known about their resistance to glycation, nor on the relationship between glycation, species' life-history traits and individual fitness. Our review summarizes the scarce current knowledge on the links between glycation and life-history traits in non-conventional animal models, highlighting the predominance of avian research. We also investigate some key molecular and physiological parameters involved in glycation regulation, which hold promise for future research on fitness and senescence of individuals.
Topics: Animals; Life History Traits; Birds; Models, Animal; Glycosylation; Aging; Glycation End Products, Advanced
PubMed: 38863347
DOI: 10.1098/rsbl.2023.0601 -
Microbiology Resource Announcements Jun 2024, a member of the family and species , is an F1 cluster phage that infects mc²155. The Maravista genome has 61.3% GC content, is 60,140 bp in length, and encodes 104...
, a member of the family and species , is an F1 cluster phage that infects mc²155. The Maravista genome has 61.3% GC content, is 60,140 bp in length, and encodes 104 putative genes. Maravista encodes two putative glycosyltransferases, suggesting glycosylation of its capsid protein.
PubMed: 38860805
DOI: 10.1128/mra.00502-24 -
American Journal of Cancer Research 2024Chemotherapy is the principal treatment for advanced cancer patients. However, chemotherapeutic resistance, an important hallmark of cancer, is considered as a key... (Review)
Review
Chemotherapy is the principal treatment for advanced cancer patients. However, chemotherapeutic resistance, an important hallmark of cancer, is considered as a key impediment to effective therapy in cancer patients. Multiple signaling pathways and factors have been underscored to participate in governing drug resistance. Posttranslational modifications, including ubiquitination, glycosylation, acetylation and phosphorylation, have emerged as key players in modulating drug resistance in gynecological tumors, such as ovarian cancer, cervical cancer and endometrial cancer. In this review article, we summarize the role of ubiquitination in governing drug sensitivity in gynecological cancers. Moreover, we describe the numerous compounds that target ubiquitination in gynecological cancers to reverse chemotherapeutic resistance. In addition, we provide the future perspectives to fully elucidate the mechanisms by which ubiquitination controls drug resistance in gynecological tumors, contributing to restoring drug sensitivity. This review highlights the complex interplay between ubiquitination and drug resistance in gynecological tumors, providing novel insights into potential therapeutic targets and personalized treatment strategies to overcome the bottleneck of drug resistance.
PubMed: 38859858
DOI: 10.62347/WYKZ9784