Search bioRxiv⌕ Search

Biology subjects

Nemati, A.

Publications and source records attributed to Nemati, A..

4 recordsLinked to original sources

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↗

Developmental remodeling of ping-pong piRNA amplification in the vertebrate female germline

The piRNA pathway silences transposable elements (TEs) in the germline, and the ping-pong amplification cycle is the hallmark of this defense.In the male germline, ping-pong is most active during a meiotic window of spermatogenesis, yet its developmental profile in the vertebrate female germline remains less well explored. Most profiling has used adult ovary and mature oocytes, stages at which piRNA pathway components are reported to be low. To address this, we generated matched strand-specific RNA-seq and small RNA-seq from pre-meiotic (E10.5) and meiotic entry (E16.5) chicken ovary, used published single-cell data to track germ-cell composition across the same window, and extended the analysis to the mature chicken ovary and to zebrafish across developmental stages. Ping-pong amplification increases at meiotic entry compared to the pre-meiotic stage across TE classes. In the mature ovary, the signature weakens, and the remaining ping-pong pairs are preferentially associated with LTR/ERV retroelements. We show that activation of a meiotic entry transcriptional program in an in vitro chicken primordial germ cell model increases the fraction of piRNA-sized reads with a partner exhibiting a 10-nt 5' overlap and increases the 1U signature of piRNA-sized reads, consistent with meiotic priming promoting piRNA biogenesis. The zebrafish ovary shows a similar meiosis-associated amplification and preferential targeting of LTR/ERV retroelements at maturity, while carrying roughly 5.7-fold more TE sequences. Similar patterns in two lineages that diverged approximately 430 million years ago suggest that germline development shapes both the timing of ping-pong amplification and the TE classes preferentially associated with it.

developmental biology↗

BMP2 signaling cooperates with retinoic acid to activate a meiotic-entry transcriptional program in chicken primordial germ cells

The initiation of meiosis in germ cells is largely regulated by extrinsic cues from the gonadal environment, but the logic of these signals remains poorly understood in non-mammalian vertebrates. Retinoic acid has long been considered a principal meiosis-inducing signal, yet recent genetic and reconstitution studies indicate that retinoic acid alone is insufficient. In mice, bone morphogenetic protein 2 cooperates with retinoic acid to establish the oogenic program through the bone morphogenetic protein-responsive transcriptional regulator Zglp1, but whether this regulatory logic is conserved beyond mammals is unknown. Here, using cultured chicken (Gallus gallus) primordial germ cells, we show that bone morphogenetic protein 2 cooperates with retinoic acid to promote a meiotic-entry transcriptional program. Retinoic acid alone induced a limited retinoic acid-responsive state, whereas combined treatment reduced the primordial germ cell program and activated early meiotic genes. The resulting transcriptome matched the premeiotic-to-meiotic-entry transition of the embryonic ovary in a single-cell atlas of chicken germ cells. We also generated a genome-edited primordial germ cell line carrying an SYCP3 promoter-green fluorescent protein reporter as a platform for dissecting meiotic-entry signals in culture. Comparative genomic analysis revealed Gallus-specific pseudogenization of ZGLP1, which is intact in closely related galliform species. Retinoic acid and bone morphogenetic protein may therefore act through a different downstream regulator in chicken. Article summaryEggs and sperm are produced by meiosis, a specialized cell division that starts during embryonic development. Retinoic acid, a signal derived from vitamin A, was long thought to be enough to start meiosis, but on its own it is not. In mice, a second signal, bone morphogenetic protein 2 (BMP2), works alongside retinoic acid to push germ cells toward the egg-producing program. We asked whether birds use the same combination. Giving both signals to chicken primordial germ cells in culture switched on genes for egg development and for the first steps of meiosis; retinoic acid alone did not. Birds and mammals last shared an ancestor more than 300 million years ago, so the pairing of these two signals appears to be an old feature of vertebrate germ cells. The cells stopped short of completing meiosis, which means other signals are still missing. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=169 SRC="FIGDIR/small/740788v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@10b8b22org.highwire.dtl.DTLVardef@db9a08org.highwire.dtl.DTLVardef@15d9726org.highwire.dtl.DTLVardef@16e4dd3_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

The identification of a SARs-CoV2 S1 protein derived peptide with super-antigen-like stimulatory properties on T-cells

Severe COVID-19 can trigger a cytokine storm, leading to acute respiratory distress syndrome (ARDS) with similarities to superantigen-induced toxic shock syndrome. An outstanding question is whether SARS-CoV-2 protein sequences can directly induce inflammatory responses. In this study, we identify a region in the SARS-CoV-2 S2 spike protein with sequence homology to bacterial super-antigens (termed P3). Computational modeling predicts P3 binding to sites on MHC class I/II and the TCR that partially overlap with sites for the binding of staphylococcal enterotoxins B and H. Like SEB and SEH peptides, P3 stimulated 25-40% of human CD4+ and CD8+ T cells, increasing IFN-{gamma} and granzyme B production. viSNE and SPADE profiling identified overlapping and distinct IFN-{gamma} and GZMB subsets. The super-antigenic properties of P3 were further evident by its selective expansion of T cells expressing specific TCR V and V{beta} chain repertoires. In vivo experiments in mice revealed that the administration of P3 led to a significant upregulation of proinflammatory cytokines IL-1{beta}, IL-6, and TNF-. While the clinical significance of P3 in COVID-19 remains unclear, its homology to other mammalian proteins suggests a potential role for this peptide family in human inflammation and autoimmunity.

immunology↗