Biology subjects

Gao, Y.-Q.

Publications and source records attributed to Gao, Y.-Q..

4 recordsLinked to original sources

bioRxiv2025

Toxoplasma gondii disrupts vitamin B and K2 biosynthetic pathways in feline gut microbiota: microbial adaptation

Vitamins B and K2 (menaquinone) are critical for microbial and host processes, but their biosynthesis in feline gut microbiota and modulation by Toxoplasma gondii remain unclear. We assembled 1,553 high-quality feline intestinal bacterial genomes from metagenomic and public data to study vitamin B and K2 biosynthesis. We identified 86,829 genes and 159 enzymes, revealing regional differences in gene and species diversity for vitamin production. Among these, 782 genomes supported de novo synthesis of at least one vitamin. T. gondii infection altered synthesis pathways: early infection boosted pyridoxine and riboflavin synthesis in the small intestine, while menadione synthesis declined in both intestines. Actinomycetota and Campylobacterota were key to menaquinone biosynthesis, with T. gondii disrupting canonical pathways and activating alternatives. These findings shed light on the complex interplay between host, parasite, and microbiota in shaping vitamin biosynthesis, offering new perspectives for maintaining feline gut health during parasitic infection.

microbiology↗

bioRxiv2025

Integrated metagenome-resolved profiling of the resistome, virulome, and mobilome in the gut microbiota of wild birds

Wild birds, with their extensive geographic distributions and high mobility, are increasingly recognized as important players in the dissemination of antimicrobial resistance. Their gut microbiota, shaped by exposure to diverse environments, may act as both reservoirs and vectors of antibiotic resistance genes (ARGs), virulence factor genes (VFGs), and mobile genetic elements (MGEs). In this study, we reconstructed 2,516 high-quality metagenome-assembled genomes (MAGs) from 718 gut metagenomes of wild birds to comprehensively profile their resistome and virulome. We identified 5,596 ARG-encoding proteins across 389 distinct ARG types, with multidrug resistance emerging as the most dominant category. Escherichia coli was the principal carrier of ARGs, and genes conferring resistance to elfamycin antibiotics via target alteration were notably widespread--indicating persistent antibiotic selection pressures in avian habitats. Co-occurrence analyses revealed extensive genetic linkage between ARGs, VFGs, and MGEs. Critically, we detected 25 ARG-MGE co-localization events within 5-kilobase genomic regions, highlighting a strong potential for horizontal gene transfer and accelerated resistance dissemination within microbial communities. Of particular concern was the detection of the tetX1 gene--conferring resistance to tigecycline, a last-resort antibiotic--in the gut microbiota of Chroicocephalus ridibundus and Cygnus cygnus. This finding strongly implicates anthropogenic pollution in the spread of clinically relevant ARGs into wildlife and emphasizes the risk of environmental transmission to other hosts, including humans. These results underscore the critical ecological role of wild birds in the global antimicrobial resistance network. As both reservoirs and potential vectors of ARGs, they represent a significant but under-monitored interface between environmental and clinical resistance pathways. Enhanced surveillance and mitigation strategies targeting wildlife are urgently needed to curb the environmental propagation of antimicrobial resistance.

microbiology↗

bioRxiv2024

Organ-specific electrophile responsivity mappingin live C. elegans

Proximity labeling technologies are limited to indexing localized protein residents. Such data-- although valuable--cannot inform on small-molecule responsivity of local residents. We here bridge this gap by demonstrating in live C. elegans how electrophile-sensing propensity in specific organs can be quantitatively mapped and ranked. Using this method, >70% of tissue-specific responders exhibit novel responsivity, independent of tissue-specific abundance. One responder, cyp-33e1--for which both human and worm orthologs are electrophile responsive--marshals stress-dependent gut functions, despite manifesting uniform abundance across all tissues studied. Cyp-33e1s localized electrophile responsivity operates site-specifically, triggering multifaceted responses: electrophile sensing through the catalytic-site cysteine results in partitioning between enzyme inhibition and localized production of a critical metabolite that governs global lipid availability, whereas a rapid dual-cysteine site-specific sensing modulates gut homeostasis. Beyond pinpointing chemical actionability within local proteomes, tissue-specific electrophile responsivity mapping illuminates otherwise intractable locale-specific metabolite signaling and stress response programs influencing organ-specific decision-making. IN BRIEFContext-specific protein reactivity is a cornerstone of biological stress responsivity, and thus has important ramifications for drug discovery; no current method can inform on these parameters. Here we debut a method that cartographs locale-specific actionability to reactive metabolites; Cyp-33e1, a gut-specific responder, emerged to partition between electrophile-driven localized enzymatic turnover that triggers gut-specific metabolite production shaping global lipid storage, and localized electrophile sensing that marshals global stress response. HIGHLIGHTSO_LILocalis-REX maps organ-specific electrophile-responsive proteins in worms C_LIO_LIHits are neither identified by organ-specific Ultra-ID nor biased by localized expression C_LIO_LIHits are enriched in proteins functionally relevant to stress-related phenotypes C_LIO_LILocalized responsivity of gut-specific hit, cyp-33e1, shapes global lipid availability C_LI

molecular biology↗

bioRxiv2019

CTCF-mediated Chromatin Structures Dictate the Spatio-temporal Propagation of Replication Foci

Mammalian DNA replication is initiated at numerous replication origins, which are clustered into thousands of replication domains (RDs) across the genome. However, it remains unclear whether the replication origins within each RD are activated stochastically. To understand how replication is regulated at the sub-RD level, we directly visualized the spatio-temporal organization, morphology, and in situ epigenetic signatures of individual replication foci (RFi) across S-phase using super-resolution stochastic optical reconstruction microscopy (STORM). Importantly, we revealed a hierarchical radial pattern of RFi propagation that reverses its directionality from early to late S-phase, and is diminished upon caffeine treatment or CTCF knockdown. Together with simulation and bioinformatic analyses, our findings point to a CTCF-organized REplication Propagation (CoREP) model. The CoREP model suggests a non-random selection mechanism for replication activation mediated by CTCF at the sub-RD level, as well as the critical involvement of local chromatin environment in regulating replication in space and time.

cell biology↗