Biology subjects

Zhi, Q.

Publications and source records attributed to Zhi, Q..

3 recordsLinked to original sources

bioRxiv2026

Global transmission architecture of VIM carbapenemases reveals host-specific dissemination strategies

Carbapenemase-producing Gram-negative bacteria carrying Verona integron-encoded metallo-{beta}-lactamase (VIM) pose a persistent global threat, yet the mechanisms driving their worldwide dissemination remain poorly resolved. We analysed 5,617 blaVIM-positive genomes collected from 73 countries or regions across six continents between 1999 and 2025 to reconstruct the global epidemiology and transmission architecture of VIM carbapenemases. Forty VIM variants were identified across 16 bacterial genera, revealing marked host preferences and temporal shifts. VIM-2 dominated global circulation, whereas VIM-1 and VIM-4 remained prominent among Enterobacterales. Strikingly, VIM spread followed distinct host-specific evolutionary strategies. In Pseudomonas aeruginosa, dissemination was largely clone-driven, with high-risk lineages ST111 and ST235 supporting long-term persistence through lineage expansion and stable inheritance. By contrast, Enterobacterales were dominated by horizontal transmission through broad-host-range IncHI2A, IncA, and IncC plasmids, although only a limited subset of plasmid-VIM combinations achieved intercontinental spread. Among 2,828 loci with sufficient flanking sequence, 96.2% were embedded within integrative genetic elements, frequently nested with insertion sequences and phage-related elements, revealing a multilayered mobile-element network underlying VIM persistence. Structural analyses showed a highly conserved metallo-{beta}-lactamase scaffold but recurrent diversification near substrate-interacting residues, particularly positions 224 and 228. Shared genetic clusters between human-associated and environmental isolates further suggested cross-niche circulation. Together, these findings establish a hierarchical, host-dependent framework for global VIM dissemination, integrating clonal expansion, plasmid transfer, and nested mobile genetic elements. ImportanceBy analysing 5,617 blaVIM-positive genomes worldwide, this study reveals a host-dependent transmission architecture of VIM carbapenemases. In P. aeruginosa, VIM dissemination is mainly driven by expansion of successful high-risk clones, particularly ST111 and ST235, whereas in Enterobacterales it is primarily mediated by broad-host-range plasmids enabling cross-species transfer. Global VIM spread is not driven by a single dominant pathway but by a limited number of successful clone-plasmid-mobile element combinations, while most genetic backgrounds remain regionally restricted. These findings define a hierarchical transmission model of VIM evolution and provide insights for genomic surveillance and targeted control of metallo-{beta}-lactamase-mediated antimicrobial resistance.

microbiology↗

bioRxiv2022

DNA binding domain undergoes dynamic and selective protein-protein interactions to facilitate CTCF insulation

CTCF is required for three-dimensional chromatin organization and a predominant insulator protein. However, its roles in insulating enhancers have not been fully explained in 3D nuclear organization. Here, we found that the CTCF DNA binding domain (DBD) forms dynamic self-interacting clusters. We next investigated the spatial relationships between these clusters and other transcription regulators with a light-induced imaging system. Strikingly, CTCF DBD clusters were found to incorporate other insulator proteins but are not coenriched with transcriptional activators in the nucleus. This property is not observed in other domains of CTCF or the DBDs of other transcription factors. Moreover, endogenous CTCF shows a phenotype consistent with the DBD by forming small protein clusters and interacts less transcriptional activators bound, CTCF motif arrays. Our results reveal an interesting phenomenon that CTCF DBD interacts with insulator proteins and selectively localizes to nuclear positions with lower concentrations of transcriptional activators, providing new insights into the insulation function of CTCF.

molecular biology↗

bioRxiv2018

The kinetochore protein Spc105, a novel interaction partner of LaeA, regulates development and secondary metabolism in Aspergillus flavus

Nuclear protein LaeA is known as the global regulator of secondary metabolism in Aspergillus. LaeA connects with VeA and VelB to form a heterotrimeric complex, which coordinates fungal development and secondary metabolism. Here, we describe a new interaction partner of LaeA, the kinetochore protein Spc105, from the aflatoxin-producing fungus Aspergillus flavus. We showed that in addition to involvement in nuclear division, Spc105 is required for normal conidiophore development and sclerotia production of A. flavus. Moreover, Spc105 positively regulates the production of secondary metabolites such as aflatoxin and kojic acid, and negatively regulates the production of cyclopiazonic acid. Transcriptome analysis of the{Delta} spc105 strain revealed that 23 backbone genes were differentially expressed, corresponding to 19 of the predicted 56 secondary metabolite gene clusters, suggesting a broad regulatory role of Spc105 in secondary metabolism. Notably, the reduced expression of laeA in our transcriptome data led to the discovery of the correlation between Spc105 and LaeA, and double mutant analysis indicated a functional interdependence between Spc105 and LaeA. Further, yeast two-hybrid (Y2H) and GST pull-down assays revealed that Spc105 interacts directly with the S-adenosylmethionine (SAM)-binding domain of LaeA, and that the leucine zipper motif in Spc105 is required for this interaction. The Spc105-LaeA interaction identified in our study indicates a cooperative interplay of distinct regulators in A. flavus, providing new insights into fungal secondary metabolism regulation networks.\n\nAuthor summaryThe worldwide concern on agriculture and food safety due to aflatoxin contamination has prompted increasing interest in understanding aflatoxin biosynthesis regulation that has become a model for exploring secondary metabolism regulation in fungi. In Aspergillus, the nuclear protein LaeA is considered as a global regulator of secondary metabolism that forms a regulatory unit with VeA and VelB. LaeA is proposed to control secondary metabolism epigenetically through altering the chromatin structure for gene expression, however, the exact mechanism is still enigmatic. Here we identified a new interaction partner of LaeA, a kinetochore protein Spc105, in aflatoxigenic Aspergillus flavus. We presented a regulatory role of this kinetochore protein in fungal development and aflatoxin biosynthesis for the first time, and demonstrated its interdependent relationship with LaeA. The finding that such a conserved cell division related gene regulates A. flavus secondary metabolism will offer new insights into the fungal secondary metabolism regulation and improve our understanding of LaeA involved networks.

microbiology↗