Biology subjects

Dadvar, A.

Publications and source records attributed to Dadvar, A..

4 recordsLinked to original sources

bioRxiv2026

Cross-Serogroup Analysis of Representative Top-Seven Shiga toxin-producing Escherichia coli Plasmids Reveals Lineage-Specific Patterns

Plasmids play a significant role in shaping the pathogenic potential of Shiga toxin-producing Escherichia coli (STEC) by encoding virulence and adaptive genes that complement chromosomal determinants. While plasmid-encoded factors such as ehxA, espP, katP, and toxB are known to enhance intestinal colonization and host interaction, the diversity and evolutionary patterns of STEC plasmids remain insufficiently characterized. Most previous studies have focused on single serogroups, particularly O157, leaving cross-serogroup comparisons largely unexplored. To address this gap, we conducted an in-depth investigation of 109 complete plasmid sequences (1.5-187 kb) from the "Top Seven" STEC serogroups (O26, O45, O103, O111, O121, O145, and O157), retrieved from NCBI, to examine their structural organization, virulence composition, resistance patterns, mobility potential, and evolutionary dynamics. Our analysis revealed the dominance of F-type plasmids carrying IncFIB and IncFII replicons across serogroups, along with lineage-specific associations with major virulence genes. By examining the enterohemolysin operon across ehxA-positive plasmids, we identified a highly conserved structural framework maintained across 92.5% of analyzed sequences, with minimal variation. We further characterized antimicrobial resistance gene distribution, finding that only 11% of plasmids (12/109) carried such genes, of which 92% were multidrug-resistant. Analysis of mobility features revealed that predicted conjugative potential and MOBF-type relaxases varied considerably among serogroups. The 32 plasmids without virulence or resistance cargo carried at most colicin determinants, yet all received a predicted mobility class, with conjugative machinery confined to plasmids above 37 kb. At the plasmid level, serogroups O26/O103 are closely related and carry relatively high-risk virulence profiles, while the O121/O145 group exhibits moderate virulence gene inventories. The O45/O111 group is further distinguished by its transfer features, while O157 strains form a distinct clade with the broadest array of plasmid-encoded high-risk virulence genes.

microbiology↗

bioRxiv2025

Scalable expansion and hepatic zone maturation of hepatic progenitor cells from human pluripotent stem cells

Scalable generation of functionally mature hepatocytes from human pluripotent stem cells (hPSCs) is vital for regenerative medicine, disease modeling, and drug screening. We present a modular differentiation platform that enables serial expansion and cryopreservation of hepatic progenitors (hepatoblasts; HBs), supporting efficient downstream maturation. By modulating bile acid signaling with FGF19 and culturing under hypoxia, we preserved HB proliferation and bipotency. Subsequent thyroid hormone treatment induced alpha-fetoprotein-negative, albumin-positive hepatocytes, while WNT pathway modulation promoted zonal identity, mimicking in vivo hepatic metabolic heterogeneity. Zonation was confirmed by differential drug-metabolizing enzyme activity, mitochondrial function, and enhanced engraftment in a liver injury mouse model. To evaluate translational relevance, mature hepatocytes were incorporated into extrusion-based 3D bioprinted constructs, which maintained hepatic viability and function. This integrated strategy of combining progenitor cell banking, zonation control, and tissue engineering offers a scalable and clinically relevant approach for generating functional human liver tissue suitable for therapeutic development.

cell biology↗

bioRxiv2025

Diverse horizontally transferred cellulose biosynthesis gene clusters in Escherichia coli strains

The phosphoethanolamine modified exopolysaccharide cellulose is a major extracellular matrix component of Escherichia coli and Salmonella typhimurium. Upon enhanced acute virulence, however, cellulose production can be diminished or entirely abolished. Here, we report that homologs of the bcsABC core genes of the core genome bcs cellulose biosynthesis operon and even entire bcs operons can be mobilized on plasmids and are occasionally manifested on E. coli chromosomes at alternative locations. While BcsA2 and BcsA3 cellulose synthases are restricted to the genus Escherichia, the BcsA4 cellulose synthase and the entire associated bcs gene cluster are highly similar to one of the two chromosomal bcs gene clusters harboured by Klebsiella pneumoniae. Cyclic di-GMP turnover proteins known to post-translationally regulate cellulose biosynthesis are frequently localized on bcs operon bearing plasmids. In thermotolerant meat derived E. coli 740v1 harbouring a type 4 bcs operon on a plasmid, chemical and genetic evidence indicates that cellulose is produced in M9 minimal medium and upon activation by the second messenger cyclic di-GMP, an allosteric activator of the cellulose synthase, respectively. With gene duplication and horizontal gene transfer to contribute to the multiplication of bcs operons in a number of different bacterial species, the ecological role(s) of multiplication, transfer and replacement of cellulose biosynthesis operons also in species other than E. coli still need to be unraveled.

genomics↗

bioRxiv2024

FAST-STEM: A human pluripotent stem cell engineering toolkit for rapid design-build-test-learn development of human cell-based therapeutic devices

Very recent clinical advances in stem cell derived tissue replacement and gene therapy, in addition to the rise of artificial intelligence-aided scientific discovery, have placed the possibility of sophisticated human cell-based therapies firmly within reach. However, development of such cells and testing of their engineered gene circuit components, has proven highly challenging, due to the need for generating stable cell lines for each design-build-test-learn engineering cycle. Current approaches to generating stable human induced pluripotent stem cell (hiPSC) lines are highly time-consuming and suffer from lack of control, poor integration efficiency, and limited functionality. Validation in clinically relevant stem cell derived tissues is also broadly lacking. Such drawbacks are prohibitive to repeatably conducting cutting-edge stem cell engineering with broad application within a realistic timeframe and will not scale with the future of regenerative medicine. We have developed FAST-STEM (Facile Accelerated Stem-cell Transgene integration with SynBio Tunable Engineering Modes), a hPSC engineering platform that drastically reduces the time to generate differentiation ready stem cell lines from several weeks to 5 days, exhibiting a ~612-fold improvement in transgene integration rate over previous methodologies. Additional FAST-STEM innovations include: (i) rapid and highly efficient transgene integration; (ii) copy number control; (iii) simultaneous or consecutive integration of multiple gene cassettes; (iv) library screen capability. In addition to this unique functional versatility, platform transportability and broad use case for stem cell-engineering was confirmed by differentiation into eight different cell types across nine different laboratories. This platform dramatically lowers the bar for integration of synthetic biology with regenerative medicine, enabling experiments which were previously deemed logistically impossible, thus paving the way for sophisticated human cell device development.

bioengineering↗