Biology subjects

ZHOU, H.

Publications and source records attributed to ZHOU, H..

4 recordsLinked to original sources

bioRxiv2023

The exotic thymidine modification 5-hydroxymethyluridine in dinoflagellate Amphidinium carterae

Dinoflagellate chromosomes are extraordinary, as their organization is independent of architectural nucleosomes unlike typical eukaryotes and shows a cholesteric liquid crystal state. 5-hydroxymethyluridine (5hmU) is present at unusually high levels and its function remains an enigma in dinoflagellates chromosomal DNA. Here, we demonstrate that 5hmU exhibits content variations in different dinoflagellates and is generated at the poly-nucleotide level through hydroxylation of thymidine. Importantly, we identified the enzyme, which is a putative dinoflagellate TET/JBP homologue, catalyzing 5hmU production using either in vivo or in vitro biochemical assay. Based on the near-chromosomal level genome assembly of dinoflagellate Amphidinium carterae, we depicted a comprehensive 5hmU landscape and found that most 5hmU peaks share a conserved TG-rich motif, and are significantly enriched in repeat elements, which mark partially overlapping regions with 5-methylcytosine (5mC) sites. Moreover, inhibition of 5hmU via dioxygenase inhibitor leads to transcriptional activation of 5hmU-marked transposable elements (TEs), implying that 5hmU appears to serve as epigenetic marks for silencing retrotransposon. Together, our results revealed the biogenesis, genome-wide landscape and molecular function of dinoflagellate 5hmU, providing mechanic insight into the function of this enigmatic DNA mark.

molecular biology↗

bioRxiv2022

Environmental factors shape the culturable bacterial diversity in deep-sea water and surface sediments from the Mariana Trench

Hailed as "The Fourth Pole", the Mariana Trench is the deepest part of the ocean. The microbial diversity in it is extremely complicated, which might be caused by the unique environmental factors such as high salinity, low temperature, high hydrostatic pressure, and limited nutrition. Based on 4 seawater samples and 4 sediment samples obtained from the Mariana Trench, we isolated and fostered the microorganism clones with kinds of culture mediums and high-throughput culturing. By using the molecular identification methods based on PCR of 16S rDNA and ITS gene, 1266 bacterial strains in total were isolated and identified, which affiliated to 7 classes, 16 orders, 25 families and 36 genera in four phyla : Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes. Strains in genera Halomonas, Pseudoaltermonas were the dominant bacteria isolated from the samples. With Mantel tests on the sample-environmental parameter matrix, the sample-environmental organic matter diversity matrix and the sample-microbial diversity matrix, we concluded that the environmental parameters and the organic matters in the condition can shape the culturable bacterial diversity in deep-sea water and surface sediments from the Mariana Trench.

microbiology↗

bioRxiv2021

Single-shot rAAV5-based Vaccine Provides Long-term Protective Immunity against SARS-CoV-2 and Its Variants

The COVID-19 pandemic and the SARS-CoV-2 with its variants have posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against the SARS-CoV-2 variants. Therefore, novel vaccines to match current mutated viral lineages with long-term protective immunity are urgently in demand. In the current study, we for the first time designed a recombinant Adeno-Associated Virus 5 (rAAV5)-based vaccine named as rAAV-COVID-19 vaccine (Covacinplus) by using RBD-plus of spike protein with both the single-stranded and the self-complementary AAV5 delivering vectors (ssAAV5 and scAAAV5), which provides excellent protection from SARS-CoV-2 infection. A single dose vaccination induced the strong immune response against SARS-CoV-2. The induced neutralizing antibodies (NAs) titers were maintained at a high peak level of over 1:1024 even after more than one year of injection and accompanied with functional T-cells responses in mice. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines exhibited high levels of serum NAs against current circulating variants including variants Alpha, Beta, Gamma and Delta. SARS-CoV-2 virus challenge test showed that ssAAV5-RBD-plus vaccine protected both young and old age mice from SARS-CoV-2 infection in the upper and the lower respiratory tracts. Moreover, whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genome of the vaccinated mice after one year vaccination, demonstrating excellent safety of the vaccine. Taken together, this study suggests that rAAV5-based vaccine is powerful against SARS-CoV-2 and its variants with long-term protective immunity and excellent safety, which has great potential for development into prophylactic vaccination in human to end this global pandemic.

immunology↗

bioRxiv2018

The role of two-component system response regulator BceR in antimicrobial resistance, virulence, biofilm formation, and stress response of group B Streptococcus.

The hypervirulent Group B Streptococcus (Streptococcus agalactiae, GBS) serogroup III clonal cluster 17 has been associated with neonatal GBS invasive disease and meningits. Serogroup III, ST283 has recently been implicated in invasive disease among non-pregnant adults in Asia. These strains cluster with strains from freshwater fishes from aquaculture and a foodborne outbreak of sepsis, especially with septic arthritis, had been linked to such consumption in Singapore in 2015. Through comparative genome analyses of invasive and non-invasive strains of ST283, we identified a truncated response regulator gene in the non-invasive strain. This two component response gene, previously named a DNA binding regulator, is conserved among GBS strains and is a homologue of Bacillus subtilis BceR, the response regulator of the BceRSAB system. Loss of function of the BceR response gene in the invasive GBS strain demonstrated bacitracin susceptibility in{Delta} BceR mutant with MICs of 256-fold and four-fold reduction in bacitracin and human cathelicin LL-37 compared to wild type and complementation strains. Upregulation of dltA of wild type strain vs{Delta} BceR mutant was demonstrated (p<0.0001), and was previously shown in Staphylococcus aureus to resist and repel cationic peptides through excess positive charges with D-alanylation of teichoic acids on the cell wall. In addition,{Delta} BceR mutant was less susceptible under oxidative stress under H2O2 stress when compared to wild type strain (p<0.001) and inhibited biofilm formation (p<0.05 and p < 0.0001 for crystal violet staining and cfu counts). The{Delta} BceR mutant also showed reduced mortality as compared to wild type strain (p<0.01) in a murine infection model. Taken together, BceRS is involved in bacitracin and antimicrobial peptide resistance, survival under oxidative stress, biofilm formation and play an important role in the virulence of GBS.\n\nAuthor SummaryTwo-component systems (TCSs) play an important role in virulence in bacteria, and are involved in detecting environmental changes. Although S. agalactiae was reported to contain more predicted TCSs than Streptococcus pneumoniae, few have been studied in detail. In this work, comparative genomic analysis of GBS invasive (hyper-virulent) and non-invasive serotype III-4 strains were performed to determine any gene differences that may account for severity of disease in humans. BceR-like TCS was selected and suspected to be involved in virulence, and thus BceR was deleted in a hyper-virulent GBS serotype III-4 strain. We demonstrated that this BceR-like TCS is involved in GBS virulence and induced proinflammatory host immune responses. Our study of TCS BceR may guide further research into the role of other TCSs in GBS pathogenicity, and further explore therapeutic targets for GBS disease.

microbiology↗