Biology subjects

Parajuli, A.

Publications and source records attributed to Parajuli, A..

3 recordsLinked to original sources

bioRxiv2026

Allelic Diversity and Core Conservation of Type III Effectors Across Xanthomonads Causing Bacterial Spot of Pepper and Tomato

Bacterial spot of tomato and pepper (BST/P) is an economically devastating disease caused by four distinct Xanthomonas pathogens: X. euvesicatoria pv. euvesicatoria (Xe), X. euvesicatoria pv. perforans (Xp), X. hortorum pv. gardneri (Xg), and X. vesicatoria (Xv). A key component of virulence in these pathogens is the type III secretion system (T3SS), which delivers type III effector (T3E) proteins into host plant cells. To comprehensively characterize T3E repertoires and assess the stability of core effectors at a population scale, we evaluated a global dataset comprising 1,037 quality-filtered genomes, including 585 Xp, 350 Xe, 69 Xg, and 33 Xv strains. Across this collection, genes for six effectors were present in 100% of the examined genomes (XopK, XopL, XopM, XopN, XopX, and XopZ1) and an additional four effectors in [≥]95% of genomes (XopK, XopL, XopM, XopN, XopX, and XopZ1). Xp and Xe populations maintained large total effector repertoires with extensive allelic variation, displaying exceptional polymorphism within XopD and XopAD. In contrast, Xg and Xv exhibited highly stable effector profiles with markedly reduced allelic diversification across geographic regions and decades. Disruptive mutations, including early stop codons and frameshifts mutations, in genes for XopAZ, XopAF, and XopAR were prevalent across specific pathogens pointing to ongoing pseudogenization and targeted gene loss. These findings provide a high-resolution characterization of the conserved and variable components of the BST/P pathogen effector arsenal and serve as a foundation for monitoring population evolution and breeding durable disease resistance to multiple pathogens.

genomics↗

bioRxiv2024

Longitudinal blood microsampling and proteome monitoring facilitate timely intervention in experimental type 1 diabetes

Symptoms of immune-mediated diseases (IMIDs) typically appear after irreversible tissue damage, making early interventions based on pre-symptomatic indicators crucial. Current efforts to identify molecular markers of early disease lack the resolution, convenience and cost efficiency required to prevent irreversible tissue damage. Analyzing frequently self-collected samples, such as dried blood spots (DBS), could enable the earlier detection of diseases, identify disease-predictive markers and facilitate tailored interventions. To test this, we regularly microsampled a mouse model infected with a type 1-diabetes (T1D)-associated virus. This longitudinal DBS sample collection was analyzed for 92 circulating proteins, revealing transient molecular changes in virus-infected animals that would have been missed with less frequent sampling. Machine learning predicted infection status after day 2 post-infection with >90% accuracy, enabling well-timed treatment of virus-infected animals and diabetes prevention. Our study demonstrates the utility of frequent blood microsampling to monitor disease during the pre-symptomatic phase, allowing for timely interventions. TeaserFrequent blood microsampling detects early biomarkers, enabling timely intervention in immune-mediated diseases

systems biology↗

bioRxiv2024

Production, analysis, and safety assessment of a soil and plant-based natural material with microbiome- and immune-modulatory effects

Reduced contact with the microbiota from the natural environment has been suggested to contribute to the rising incidence of immune-mediated inflammatory disorders (IMIDs) in the western, highly urbanized societies. In line with this, we have previously shown that exposure to environmental microbiota in the form of a blend comprising of soil and plant-based material (biodiversity blend; BDB) enhances the diversity of human commensal microflora and promotes immunoregulation that may be associated with a reduced risk for IMIDs. To provide a framework for future preclinical studies and clinical trials, this study describes how the preparation of BDB was standardized, its microbial content and safety assessments. Multiple batches of BDB were manufactured and microbial composition analyzed using 16S rRNA gene sequencing. We observed a consistently high alpha diversity and relative abundance of bacteria normally found in soil and vegetation. We also found that inactivation of BDB by autoclaving effectively inactivates human and murine bacteria, viruses and parasites. Finally, we demonstrate that experimental mice prone to develop IMIDs (non-obese diabetic, NOD, mouse model) can be exposed to BDB without causing adverse effects on animal health and welfare. Our study lays the foundation for a safe, sustainable, and affordable way to mimic exposure to natural microbiota that has the potential to have enormous health- and socio-economic impacts.

microbiology↗