Biology subjects

Dahiya, P.

Publications and source records attributed to Dahiya, P..

6 recordsLinked to original sources

bioRxiv2026

Molecular Alterations of Bovine Serum Albumin Induced by the Food Dye Acid Yellow 23: A Mechanistic Study

The widespread use of synthetic food dyes, such as Acid Yellow 23 (AY 23), in the food, cosmetics, and pharmaceutical industries raises questions about their potential effects on biological systems and public health. The concentration-dependent interaction between AY 23 and bovine serum albumin (BSA), a crucial model protein for understanding pharmacokinetics and protein-ligand behaviour, was examined in this study. We demonstrate that, under physiological conditions, increasing dye concentrations from 50 {micro}M to 200 {micro}M results in notable conformational changes, increased surface hydrophobicity, and protein aggregation using a multimodal biophysical approach that includes fluorescence spectroscopy. Direct visualisation verified these structural changes and aggregate formation, whereas hemolytic assay confirmed the high hemolytic nature of AY 23-induced fibrils. Additionally, this study provides a mechanistic basis for the toxicological effects of AY 23, underscoring the implications of food dyes for public health. HighlightsO_LIAcid Yellow 23 (AY 23) modulates Bovine Serum Albumin (BSA) structure and leads to aggregation under physiological conditions. C_LIO_LIStructural alteration is followed by binding of AY 23 at the hydrophobic regions of BSA, perturbing the globular protein into fibrillar aggregates. C_LIO_LI{middle dot} Confirmational changes induced by AY 23 in the BSA via interaction with Asp108, Pro110 and Ala193. C_LIO_LIFibrils formed after AY 23 interaction are observed to be hemolytic in nature. C_LIO_LIMolecular mechanism of AY 23-mediated fibrillation of BSA was assessed. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/737154v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@241c95org.highwire.dtl.DTLVardef@d0a03aorg.highwire.dtl.DTLVardef@c7445borg.highwire.dtl.DTLVardef@58cf7c_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

The PPE2 protein of Mycobacterium tuberculosis is responsible for the development of hyperglycemia and insulin resistance during tuberculosis

Diabetes is a known risk factor for tuberculosis (TB), but clinical evidences suggest that TB itself can induce hyperglycaemia and insulin resistance, though the underlying mycobacterial factors are not known. Herein, we implicate PPE2, a secretory PE/PPE family protein of Mycobacterium tuberculosis (Mtb), as a key modulator of adipose tissue physiology that contributes to the development of insulin resistance. In mice, PPE2 caused fat loss, adipocyte hypertrophy, immune cell infiltration, impaired glucose tolerance, reduced expression of PPAR-{gamma}, C/EBP-, adiponectin and higher insulin resistance. Transcriptomic analysis revealed PPE2 altered expression of genes associated with chemokine/cytokine, ribosomal biogenesis and lipase signaling. PPE2 induced lipolysis by activating cAMP-PKA-HSL axis, increased circulating free fatty acids, a feature also observed in TB patient sera. Interestingly, PPE2-immunization mitigated these effects, suggesting its potential as a subunit vaccine. Overall, this study identifies PPE2 as a key link between Mtb-infection, adipose tissue dysfunction and insulin resistance.

microbiology↗

bioRxiv2025

PE11 promotes intracellular persistence of Mycobacterium tuberculosis by inhibiting autophagy and lysosomal biogenesis by targeting the FLCN-lactate-TFEB signaling axis

Mycobacterium tuberculosis (Mtb) employs multiple virulence factors, including cell wall-associated proteins, to evade host immune responses. PE11, a cell wall-localized esterase, contributes to Mtb persistence by facilitating cell wall remodelling and resistance to acidic and antibiotic stress. Herein we describe a novel role of PE11 in subverting host autophagy through disruption of TFEB-mediated lysosomal function. PE11 promotes FLCN-dependent depletion of intracellular lactate to destabilize TFEB and thereby downregulate genes essential for autophagic flux and lysosomal acidification. Using a PE11-deficient Mtb strain, we demonstrate that PE11 targets the FLCN-lactate axis to regulate TFEB stability. Exogenous lactate supplementation restored TFEB stability, enhanced lysosomal acidification, and significantly reduced intracellular bacterial burden. Lactate also synergized with frontline anti-tubercular drugs to improve Mtb clearance. These findings establish PE11 as a key immune evasion factor and highlight lactate as a promising host-directed therapeutic to enhance bacterial killing and reduce antibiotic-associated toxicity.

microbiology↗

bioRxiv2025

Hypoxia-Mediated Molecular Interactions of Tissue-Specific Mesenchymal Stem Cells Drive Metabolic Reprogramming and Immunomodulation in Acute Graft-versus-Host Disease

BackgroundMesenchymal stem cells (MSCs) mediate immunomodulation through various mechanisms, including apoptosis, efferocytosis, and mitochondrial transfer. Our study investigates the impact of hypoxia preconditioning on the immune metabolic reprogramming and immunomodulatory potential of MSCs in acute graft-versus-host disease (aGVHD). Additionally, we explored the differential immunomodulatory effects of tissue-specific MSCs, specifically bone marrow (BM) and Whartons Jelly (WJ), and elucidated the mechanisms underlying variability in their therapeutic efficacy. MethodsMSCs were isolated from BM and WJ and subjected to hypoxia preconditioning. Their immunometabolic programming potential was assessed by evaluating T-cell proliferation, regulatory T-cell (Treg) induction, effector T-cell differentiation toward Th2, Th9 phenotypes, and macrophage polarization, T-cell bioenergetics in the direct co-culture systems. ResultsWJ-MSCsHYP exhibited superior immunomodulatory properties compared to BM-MSCsHYP, by inhibiting T-cell proliferation, enhancing Treg induction, and promoting anti-inflammatory macrophage polarization. WJ-MSCsHYP demonstrated enhanced mitochondrial transfer to T-cell, improving mitochondrial health, reducing ROS, and promoting oxidative phosphorylation, leading to immune homeostasis. Unlike BM-MSCs, WJ-MSCs exhibited higher rates of apoptosis, which facilitated immune modulation through mechanisms independent of efferocytosis. ConclusionOur findings highlight that WJ-MSCsHYP is a superior candidate for aGVHD by utilizing apoptosis, mitochondrial transfer, and metabolic reprogramming to achieve immune regulation.

immunology↗

bioRxiv2024

IQD2 recruits KLCR1 to the membrane-microtubule nexus to promote cytoskeletal mechano-responsiveness in leaf epidermis pavement cells

Plant cells experience a variety of mechanical stresses from both internal and external sources, including turgor pressure, mechanical strains arising from heterogeneous growth between neighboring cells, and environmental factors like touch from soil, rain, or wind [1,2]. These stresses serve as signals at the cell-, tissue- and organismal level to coordinate plant growth during development and stress responses [3]. In plants, the physical cell wall-plasma membrane-microtubule continuum is proposed to be integral in transducing mechanical signals from the exterior to intracellular components [4-6]. Cortical microtubules (CMTs) rapidly reorient in response to mechanical stress to align with the maximal tensile stress direction [7,8]. Several studies proposed that CMTs themselves may act as stress sensors; the precise mechanisms involved in the regulation of CMTs and the modes of sensing, however, are still not clearly understood. Here, we show that IQD2 and KLCR1 are enriched at CMTs in proximity to the plasma membrane. IQD2, which is a bona fide microtubule-associated protein, promotes microtubule localization of KLCR1. By combining cross-linking mass spectrometry (XL-MS) and computational modeling with structure-function studies, we present first experimental insights into the composition and structure of IQD2-KLCR1 complexes. Further, we demonstrate that the IQD2-KLCR1 module is a positive regulator of microtubule mechano-responses in pavement cells. Collectively, our work identifies the IQD2-KLCR1 module as novel regulator of mechanostress-mediated CMT reorientation and provides a framework for future mechanistic studies aimed at a functional dissection of mechanotransduction at the plasma membrane-CMT interface during growth and plant morphogenesis. HighlightsO_LIIQD2 and KLCR1 localize to the plasma membrane-microtubule nexus C_LIO_LIIQD2 is required for efficient microtubule targeting of KLCR1 in planta C_LIO_LIIQD2 physically interacts with KLCR1 and microtubules C_LIO_LIThe IQD2-KLCR1 module promotes mechano-stress induced microtubule reorganization C_LI

plant biology↗

bioRxiv2024

Structure-function relationship of PE11 esterase of Mycobacterium tuberculosis with respect to its role in virulence

The lipolytic enzymes of Mycobacterium tuberculosis play a critical role in immunomodulation and virulence. Among these proteins, PE11 which also belongs to the PE/PPE family, is the smallest ([~]10.8 kDa) and play a significant role in cell wall remodelling and virulence. PE11 is established to be an esterase, but its enzymatic and structural properties are not yet characterized. In this study, using homology modelling we deduced the putative structure which shows the presence of both -helix and {beta}-sheet structures which is in close agreement with that observed by CD spectra of the purified protein. PE11 was found to contain a GX3SX4G motif homologous to canonical GxSxG motif present in many serin hydrolases. The catalytic triad appears to be located within this motif as substitution of Serine26 and Glycine31 residues abrogated its enzymatic activity. Gel-filtration chromatography data indicate that PE11 possibly exists as dimer and tetramer showing positive cooperativity for binding its substrates. In addition, PE11 esterase activity was found to be critical for cell wall remodelling, antibiotic resistance and conferring survival advantages to M. tuberculosis. Our data suggest that PE11 can be targeted for designing potential therapeutic strategies.

microbiology↗