Biology subjects

Bhattarai, K.

Publications and source records attributed to Bhattarai, K..

4 recordsLinked to original sources

bioRxiv2026

Niche-specific metabolic signatures in non-typeable Haemophilus influenzae

Non-typeable Haemophilus influenzae (NTHi) is a prominent opportunistic pathogen relevant to chronic respiratory diseases. NTHis metabolic diversity enables its survival in a wide range of environmental conditions within the host. As such, deeper research into the metabolic pathways of NTHi may open an avenue for novel therapies aimed at combating NTHi-associated respiratory diseases. Draft genome sequences from nine NTHi clinical strains from three isolation sites - ear (ear sample, ES), pharynx (pharynx sample, PS), and lower respiratory tract (Lungs) - were analyzed and annotated using RAST, PROKKA, KEGG KAAS, and antiSMASH. Pathway module coverage per-strain was computed and summarized by per-group for significant annotated metabolites. Metabolites were analyzed by LC/HRMS, identified by Metaboscape, and statistically compared using MetaboAnalyst and R software. Gene content across the tested NTHi strains was largely conserved, with limited core-genome SNP variation. Gene annotation for metabolite-related pathways revealed that all nine strains possessed largely similar sets of metabolic pathway genes, despite minor nucleotide-level differences, indicating broadly comparable metabolic capacities. In contrast, metabolomics data revealed differential metabolic profiles among the body-site groups. In a principal component analysis (PCA), the ES group was significantly separated from both the PS and Lung groups, which overlapped considerably. Detailed metabolite analyses showed that inosine, hypoxanthine, and uracil were highly significant in the ES group compared to the PS and Lung groups. For the first time, our study sheds light on the extent of metabolic differences associated with NTHi inhabiting diverse host niches. The observed metabolic differences suggest that NTHi may modulate its metabolism in a site-specific manner that is affected by environmental factors. These findings add to our understanding of how NTHi metabolism contributes to site-specific colonization. Author summaryHaemophilus influenzae is widely recognized as a causative agent of meningitis and pneumonia. In particular, H. influenzae strains with a polysaccharide capsule--known as H. influenzae type b (Hib)--were historically a major cause of invasive disease. However, Hib has been largely eradicated following implementation of the Hib vaccine. Nonetheless, there are H. influenzae strains that lack this capsule and are therefore not targeted by the vaccine. These are known as non-typeable H. influenzae (NTHi). Following the decline of Hib, NTHi has rapidly occupied the ecological niche in the lower respiratory tract, becoming the most prominent pathogen in patients with chronic respiratory infections--particularly in those with chronic obstructive pulmonary disease (COPD), where it frequently triggers exacerbations. Importantly, NTHi is also a common component of the normal microbiome in healthy individuals, typically residing in the upper respiratory tract without causing disease. In our study, we investigated the metabolic characteristics of NTHi isolates obtained from different body sites in patients to better understand what distinguishes strains capable of colonizing specific anatomical niches. We successfully identified several distinct metabolic features associated with NTHi strains from the ear, pharynx, and lung. These findings may serve as a foundation for future research into patient-tailored biomarkers and targeted therapies, ultimately aiming to eradicate NTHi in chronic lung infections.

microbiology↗

bioRxiv2025

The Genetic Basis of Chloride Exclusion in Grapevines

Mediterranean regions are among the most important areas for global grape production, characterized by dry climates and frequent challenges associated with soil salinity. In these environments, chloride toxicity is a major factor limiting vine growth and fruit quality. Despite the critical role of chloride exclusion in salinity tolerance, the genetic mechanisms underlying this trait remain poorly understood. In this study, we leveraged one of the largest Vitis germplasm collections, comprising 335 accessions from 18 wild and cultivated Vitis species, to characterize natural variation in chloride exclusion. This diverse panel, which includes accessions from the southwestern United States and Mexico, captures a broad range of evolutionary adaptations to abiotic stress, providing an unprecedented opportunity to investigate the genetic basis of salinity tolerance. Using genome-wide association (GWA) and quantitative trait loci (QTL) mapping, we identified a major QTL on chromosome 8 containing candidate genes encoding cation/H exchangers (CHX), which are involved in ion transport and homeostasis. To validate these findings, we analyzed a mapping population derived from V. acerifolia longii 9018 and the commercial rootstock GRN3, confirming the chromosome 8 locus as a major determinant of chloride exclusion. Structural variant analysis revealed key non-synonymous substitutions within CHX genes, suggesting potential functional roles in salinity tolerance. Additionally, we discovered a novel QTL on chromosome 19 enriched with G-type lectin S-receptor-like serine/threonine-protein kinases, known regulators of stress signaling. By integrating extensive phenotypic and genomic data across a diverse Vitis collection, this study provides novel insights into the genetic architecture of chloride exclusion and identifies valuable candidate genes for breeding salt-tolerant rootstocks.

genetics↗

bioRxiv2024

Hyperspectral Sensing for High-Throughput Chloride Detection in Grapevines

Soil salinity affects major viticultural areas worldwide with chloride ions being the primary source of salt toxicity in grapevines. This toxicity impacts vine health and reduces fruit yield and quality. Current breeding efforts to improve grapevine salinity tolerance are limited by the low throughput of available phenotyping methods, which are time-consuming, labor-intensive, and destructive. This study demonstrated that hyperspectral proximal sensing can be utilized as a high-throughput, non-destructive screening technique to identify salinity-tolerant grapevine germplasm. The predictive abilities of two different hyperspectral devices, which varied in price, resolution, and sensitivity, were compared across 23 Vitis accessions spanning eight species. Prediction models were built using hyperspectral reflectance and leaf chloride content measured with a lab chloridometer. Three distinct approaches were studied: 1) analyzing the correlation between individual wavelengths and chloride content; 2) employing machine learning models, including Partial Least Squares Regression (PLSR), Random Forest (RF), and Support Vector Machine (SVM), utilizing all wavelengths; and 3) classification-based prediction using Partial Least Squares Discriminant Analysis (PLSDA). Multiple regions in the spectrum, including 613-660 nm, 689-696 nm, and 1357-1358 nm, showed a medium correlation (0.30-0.50) with chloride content in the leaves. PLSR was the most effective machine learning approach, demonstrating moderate predictive capability for chloride content (maximum R{superscript 2} = 0.67), though performance varied between the two devices tested. With PLSDA, predictions increased considerably, up to an accuracy of 0.97, depending on the instrument used and the spectral data transformation. Overall, the more expensive and sensitive device with a wider spectral range outperformed the more affordable, shorter-range device. However, when the prediction model was based on classes (chloride excluders vs. non-excluders) rather than chloride content, the differences in prediction abilities were minimal, with both instruments performing very well. This is promising for identifying breeding materials with chloride exclusion capabilities at low cost and high throughput.

plant biology↗

bioRxiv2023

Bioinformatics-Guided Discovery of Biaryl-Tailored Lasso Peptides

Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that feature an isopeptide bond and a distinct lariat fold. A growing number of secondary modifications have been described that further decorate lasso peptide scaffolds. Using genome mining, we have discovered a pair of lasso peptide biosynthetic gene clusters (BGCs) that include cytochrome P450 genes. Here, we report the structural characterization of two unique examples of (C-N) biaryl-containing lasso peptides. Nocapeptin A, from Nocardia terpenica, is tailored with Trp-Tyr crosslink while longipepetin A, from Longimycelium tulufanense, features Trp-Trp linkage. Besides the unusual bicyclic frame, longipepetin A receives an S-methylation by a new Met methyltransferase resulting in unprecedented sulfonium-bearing RiPP. Our bioinformatic survey revealed P450(s) and further maturating enzyme(s)-containing lasso BGCs awaiting future characterization.

biochemistry↗