Adherent-invasive Escherichia coli (AIEC) has been related to the physiopathology of Crohn’s disease, yet its pathogenic mechanisms are not completely understood. Arginine biosynthesis genes are upregulated in AIEC strains compared to non-AIEC strains present in the supernatant of infected intestinal epithelial cells, suggesting that arginine biosynthesis may be involved in AIEC pathogenicity. To test this hypothesis, the argR gene, encoding the transcriptional repressor ArgR, was deleted in the AIEC strains AIEC16 and LF82, and in E. coli Nissle 1917 and K-12 C600, leading to increased expression of arginine biosynthesis genes. Phenotypic assays and transcriptomic analyses were conducted to assess differences between mutants (ΔargR) and wild-type (WT) strains. The absence of ArgR led to a more invasive and motile AIEC LF82 strain. No differences in invasion were found for AIEC16 and the mutation led to reduced motility and biofilm formation in this strain. Transcriptomic analysis was in line with the phenotypic observations and further revealed that ArgR regulates the expression of multiple virulence-associated genes. Acid resistance genes (gad operon) were upregulated in ΔargR strains, indicating a repressive role of ArgR. Conversely, genes involved in adhesion, lipopolysaccharide biosynthesis, and iron uptake were downregulated in mutant strains, suggesting that ArgR functions as an activator for these pathways. These findings highlight ArgR as a potential modulator of multiple virulence traits, influencing the invasive and adaptive capabilities of AIEC.
Xuli Du, Ye Hu, Haimo Shen, Mengyu Li, Yuxin Wang, Yanli Bai, Shenbo Chen, Yanting Fan
Genomes obtained through imported-malaria surveillance can support source attribution and monitoring of parasite movement. However, these genomes are sampled after travel, diagnosis, reporting, and specimen availability, and may not be directly interchangeable with parasites sampled in endemic settings. Comparisons with public reference data may also be affected by geographic composition, sequencing quality, genotype filtering, and within-host infection complexity. We compared West Africa-associated P. falciparum isolates detected through China’s post-elimination malaria surveillance system with West African Pf3K and locally collected comparison isolates. We implemented country-balanced reference subsampling, a geographically restricted and quality-controlled population-structure analysis, and sensitivity analyses restricted to imported isolates with F WS >0.90 or 0.95. Population structure, within-host complexity, identity-by-descent, nucleotide diversity, gene-level F ST, and Tajima’s D were evaluated using analysis-specific variant sets. In the quality-controlled D1 analysis, 31 China-imported isolates showed a population-structure distribution that did not fully overlap with the selected West African Pf3K reference panel. This broad placement was qualitatively compatible with the high-F WS D2a subset of four imported isolates. Country-balanced reference subsampling produced similar broad PCA placement. In the D2b analysis of nine imported isolates with F WS >0.90, central gene-level F ST summaries were like those in the original analysis, whereas individual-gene estimates and Tajima’s D contrasts were sensitive to the revised filtering and sample restriction. Imported malaria genomes provide a surveillance-defined view of parasite diversity and remain useful for regional population placement and surveillance applications. However, their comparison with endemic reference panels is sensitive to dataset composition, variant filtering, and infection complexity. Imported surveillance genomes should therefore not be interpreted as unbiased or directly interchangeable proxies for parasite populations in presumed source settings. The observed differences cannot be attributed solely to surveillance pathway.
Shuang Wang, Dongliang Chen, Dawei Yang, Lei Gao, Yifan Zhang
The gut microbiota contributes to intestinal homeostasis through dynamic interactions with epithelial, immune and stromal cells. Disruption of the balance, often termed dysbiosis, has been associated with colorectal cancer (CRC). At the same time, selected commensal bacteria have shown protective effects. Toll-like receptors (TLRs) provide an important molecular interface through which host cells detect bacterial components and initiate cellular responses. This Mini Review examines current evidence that intestinal bacteria and their products modulate TLR signaling in CRC, with effects that may promote or restrain tumor development. The reported mechanisms involve CRC cells as well as immune and stromal compartments within the tumor microenvironment. The available evidence does not support assigning a fixed biological effect to a bacterial species or TLR. Instead, the reported outcomes appear to vary with the nature of the bacterial stimulus, the responding cell and the disease setting. Resolving this context dependence may clarify how host cells translate bacterial stimuli through TLRs into responses that influence CRC progression and treatment response.
