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Biomedical subjects

Shiyu Chen

Publications and source records attributed to Shiyu Chen.

3 recordsLinked to original sources

Molecular epidemiology of levofloxacin-resistant Klebsiella pneumoniae and the association of plasmid-mediated quinolone resistance genes with key biological phenotypes.

UNLABELLED: Klebsiella pneumoniae is a major opportunistic pathogen in China, yet the molecular epidemiology of quinolone resistance remains poorly characterized. This study analyzed 2,433 clinical isolates from 37 Chinese hospitals (2018-2022). The overall levofloxacin-non-susceptible (NS) rate was 53.60%, with urinary tract isolates showing higher resistance. Whole-genome sequencing identified 12 plasmid-mediated quinolone resistance (PMQR) genes. Among 1,304 NS strains, 74.54% carried at least one PMQR gene (mainly qnrS, qnrB, and aac(6')-Ib-cr), and 60.20% also had quinolone resistance-determining region (QRDR) mutations. Functional studies revealed diverse phenotypic impacts. Most PMQR genes conferred low-level resistance (minimum inhibitory concentration [MIC] = 1 mg/L), while qnrB52 and qnrB91 caused high-level resistance (MIC = 8-16 mg/L). Notably, qnrB91 reduced biofilm formation, indicating a trade-off between resistance and colonization. Growth assays showed that qnrB52, qnrB91, and qnrS1 inhibited normal growth, whereas qepA1 and qnrS1 enhanced growth under ethanol stress. Most PMQR genes (except qnrB6) attenuated bacterial adhesion. qepA1 promoted intracellular survival in macrophages, suggesting a role in chronic infection. Animal models confirmed that qnrB6, qnrB7, qnrVC6, and aac(6')-Ib-cr significantly enhanced virulence. This study is the first in China to report qnrVC6 and novel gyrA mutations (Ser83Ala/Val, Asp87Phe/His) in K. pneumoniae. It systematically reveals how PMQR genes influence infection by modulating resistance, immune evasion, and pathogenicity. These findings highlight that PMQR genes contribute not only to antibiotic resistance but also to virulence, suggesting that treatment strategies should consider specific PMQR genotypes. This research provides the largest-scale molecular epidemiological data and a theoretical basis for controlling quinolone-resistant K. pneumoniae in China. IMPORTANCE: Quinolone-resistant Klebsiella pneumoniae poses a serious threat to public health, yet the role of plasmid-mediated quinolone resistance (PMQR) genes beyond antibiotic resistance remains underexplored. In this largest-scale multicenter study in China, we analyzed 2,433 clinical isolates and discovered that PMQR genes do more than just confer drug resistance-they also influence bacterial growth, stress survival, biofilm formation, and the ability to evade or persist within host immune cells. Some PMQR genes even enhance virulence in an animal model. These findings challenge the traditional view of resistance genes as mere contributors to drug failure, revealing that they can also shape infection outcomes by altering bacterial behavior. Understanding these dual roles may guide more precise treatment strategies targeting specific PMQR genotypes.

Klebsiella pneumoniae

Characterization of age-related changes in the gut microbiome and metabolome of Kunming dogs and their associations with police performance.

BACKGROUND: Gut microbiota plays a pivotal role in regulating the host's central nervous system (CNS) activity and behavior. However, its influence on the police performance of Kunming dogs and the underlying mechanisms remain largely unexplored. This study was the first to apply multi-omics technologies to investigate the dynamic variations in gut microbiota and their metabolic profiles across different ages of Kunming dogs. Furthermore, we systematically examined the associations between these microbial alterations and police performance metrics, providing a theoretical foundation for enhancing the working capabilities of Kunming dogs through targeted modulation of intestinal microecology. RESULTS: The study showed that puppies, young dogs and adult dogs had significantly better police performance than elderly dogs, with young dogs exhibiting the highest scores. Analysis of 16S rRNA sequencing demonstrated that gut microbial diversity and stability were highest during the young dog stage, gradually declining with age. Metagenomic analysis revealed that the abundance of Lactobacillus acidophilus, Lactobacillus johnsonii, Limosilactobacillus reuteri, Ligilactobacillus animalis and Muribaculum gordoncarteri were strongly correlated with police performance. The results of metagenome-assembled genomes (MAGs) indicated that the above species have functional genes involved in GABAergic and glutamatergic synapse pathways. Furthermore, metabolomic analysis showed that differential metabolites were enriched in the neuroactive ligand-receptor interaction pathway, in which GABA (γ-aminobutyric acid), histamine and tyramine metabolites were positively correlated with the above species and police performance. CONCLUSION: The species L. acidophilus, L. johnsonii, L. reuteri, L. animalis, and M. gordoncarteri, which were enriched in the gut of puppies and young Kunming dogs, may potentially influence the nervous system through the production of neurotransmitters and neuromodulators, suggesting a possible association with police performance. Video Abstract.

Animals

Cross-kingdom genomic variation in chicken gut microbiomes: insights from China's diverse local breeds.

BACKGROUND: The gut microbiome possesses substantial genetic diversity that supports microbial adaptation, but the genomic variation patterns across its prokaryotic and viral populations remain incompletely characterized. RESULTS: Through integrated metagenomic and metatranscriptomic analysis of ten indigenous chicken breeds from China, we recovered 1527 representative prokaryotic MAGs, 37,555 representative DNA viral contigs, and 1867 representative RNA viral contigs (primarily comprising Bacillota/Bacteroidota, Uroviricota, and Lenarviricota/Pisuviricota, respectively). By integrating complementary short-read and long-read metagenomics with metatranscriptomics, we identified structural variants (SVs) and single-nucleotide variants (SNVs) in these cross-kingdom genomes. Positive SV-SNV density correlations occurred consistently across all microbial groups, indicating coordinated mutational processes. DNA viruses exhibited the highest variant prevalence (86.9% SNVs, 47.7% SVs), with temperate phages accumulating significantly more variants than virulent phages. Functionally, prokaryotic variants accumulated in carbohydrate metabolism and amino acid metabolism, while viral variants demonstrated broad metabolic hijacking. Horizontal gene transfer (HGT) was characterized by a strong virus-associated signature (69.40% of 536 events) and marked by an asymmetric pattern, with phage-to-bacteria (P-to-B) flow alone constituting 37.50% of all events. Random forest analysis revealed a strong bidirectional predictive relationship between SV and SNV densities across prokaryotic, DNA viral, and RNA viral populations, suggesting coupled genomic instability. Niche breadth emerged as a major driver of SNVs across kingdoms and was positively correlated with variant density. In prokaryotes, HGT events significantly shaped variant patterns. For viruses, genomic GC content was an important factor and consistently showed a negative correlation with SNV density in both DNA and RNA viruses. CONCLUSIONS: These findings demonstrate that coordinated mutational processes and kingdom-specific intrinsic factors drive genomic variation, with viruses serving as key genetic exchange vectors in chicken gut ecosystems. Video Abstract.

Animals