Biology subjects

Naqvi, I.

Publications and source records attributed to Naqvi, I..

5 recordsLinked to original sources

bioRxiv2025

Identification and Characterization of Outer Membrane Proteins and Membrane Spanning Protein Complexes in Brucella melitensis

Brucellosis (Malta fever) is a zoonotic disease that affects both humans and animals, including cattle, sheep, and goats. Brucella melitensis is the most virulent and clinically significant species in humans. It is a Gram-negative bacterium with three groups of outer membrane proteins (OMPs): minor OMPs (Group 1), and major OMPs (Groups 2 and 3). OMPs with {beta}-barrel architecture play important roles in nutrient transport, efflux, adhesion, and membrane biogenesis. Despite their importance, the structure, function, and interaction dynamics of several B. melitensis {beta}-barrel OMPs and associated protein complexes remain mostly unexplored. In this study, we conducted a comprehensive in silico analysis to characterize known outer membrane {beta}-barrel (OMBB) proteins and identify novel OMBBs in B. melitensis 16M. Proteins were modelled using five computational tools: AlphaFold 3, ESMFold, SWISS-MODEL, RoseTTAFold, and TrRosetta. Outer-membrane insertion of the novel OMBBs was confirmed using PPM 3.0, Protein GRAVY, DREAMM, and MemProtMD_Insane. Putative functions were predicted using structure- and sequence-based annotations. Sequence variation across 46 B. melitensis strains were identified and mapped onto the structural models. OMBB-associated protein complexes - the RND (Resistance-Nodulation-Division) efflux pumps, the lipopolysaccharide transport (Lpt) complex, and the {beta}-barrel assembly machinery (BAM) complex - were modelled, and protein-protein interactions (PPIs) were analyzed to confirm thermodynamically stable assemblies. This study presents a robust in silico strategy for exploring OMP architecture and provides valuable structural insights to support the development of diagnostics, targeted therapeutics, and vaccines against B. melitensis.

bioinformatics↗

bioRxiv2025

Design of a Multi-Epitope Vaccine using β-barrel Outer Membrane Proteins Identified in Chlamydia trachomatis

Chlamydia trachomatis is an obligate intracellular Gram-negative pathogen responsible for causing sexually transmitted infections (STIs) and trachoma. Current interventions, including screening and antibiotics, are limited due to the widespread nature of asymptomatic infections, and the absence of licensed vaccine exacerbates the challenge. In this study, we predicted outer membrane {beta}-barrel (OMBB) proteins and designed a multi-epitope vaccine (MEV) construct using identified proteins. We employed a consensus-based computational framework on the C. trachomatis D/UW-3/CX proteome and identified 17 OMBB proteins, including well-known Pmp family members and MOMP. Eight OMBB proteins were computationally characterized, which showed significant structural homology with known outer membrane proteins from other bacteria. Sequence-based annotation tools were used to determine their putative functions. B-cell and T-cell epitopes were predicted from the selected proteins. The MEV construct was designed using four cytotoxic T lymphocyte (CTL) epitopes and 29 helper T lymphocyte (HTL) epitopes predicted from six OMBB proteins, which were conserved across 106 C. trachomatis serovars. The vaccine was supplemented at the N-terminus with Cholera enterotoxin subunit B and PADRE sequence to enhance its immunogenicity. The MEV construct of 780 amino acids was antigenic, non-allergenic, non-toxic, and soluble. Secondary structure analysis revealed 95% random coils. The 3D structural model of MEV was generated and validated, confirming its structural reliability. Molecular docking between MEV and Toll-like receptor 4 (TLR4) revealed strong and stable binding interactions, supporting its potential to elicit a strong immune response. This study highlights OMBB proteins as promising immunogenic targets and presents a computationally designed MEV candidate for C. trachomatis infection.

bioinformatics↗

bioRxiv2025

Identification and Characterization of Novel Outer Membrane Proteins of Brachyspira pilosicoli

Brachyspira pilosicoli is a pathogenic, Gram-negative, spirochete bacterium that causes intestinal spirochetosis (IS) in birds, pigs, and humans and is distributed worldwide. This anaerobic intestinal bacterium colonizes the large intestine, potentially leading to colitis, diarrhoea, and decreased growth rate. Outer membrane proteins of Gram-negative bacteria play crucial roles in adhesion and host-pathogen interaction, helping the bacteria to evade the host immune system, and enhancing their virulence. However, B. pilosicoli outer membrane proteins are yet to be identified and characterized. Here, we report the computational discovery of 42 outer membrane {beta}-barrel (OMBB) proteins in B. pilosicoli proteome predicted using a consensus-based computational framework. {beta}-barrel architectures of the predicted proteins were confirmed by generating AlphaFold 3-based structural models. Structure-based functional annotation predicted putative functions for the identified OMBB proteins, including BamA homolog involved in folding and membrane insertion of OMPs, LptD homolog involved in transport of lipopolysaccharides into the OM, efflux pumps, transporters, enzymes, diffusion channels, and porins. Sequence variations across nine strains of B. pilosicoli were identified and mapped onto structural models, revealing that many of the variations were present on the surface exposed loop regions of the {beta}-barrel structures. Our in-silico analysis has identified 42 OMBB proteins, including homologs of BamA, LptD, TolC, TonB-dependent receptors, CsgG. Seven of these were identified as hypothetical proteins. Computational characterization of the predicted OMBB proteins offer insights into their potential roles in physiology, virulence, and disease pathogenesis, highlighting their potential for applications in diagnostics, vaccine development, or therapeutic interventions.

bioinformatics↗

bioRxiv2020

Faunistic study on the freshwater ciliates from Delhi, India

The ciliated protist communities show richness as well as uniqueness. This is true both for aquatic and soil ciliates. Delhi region lies in the subtropical semi-arid zone wherein the temperatures are highest in May-June and lowest in January. It also receives its monsoonal rainfall during the month of July-August. Thus, the region offers ideal conditions for the growth and proliferation of aquatic living beings. During the past three decades, a series of investigation has been carried out on the freshwater free-living ciliate fauna from fourteen sites at the river Yamuna and different freshwater bodies in Delhi. Samples were brought to the laboratory, ciliates were identified using live-cell observations and silver staining methods. A large number of Spirotrich species and a lower proportion belonging to class Heterotrichea, Litostomaea, Phyllopharyngea, Oligohymenophorea, Prostomatea, and Colpodea were identified. A total of 55 species belonging to 7 classes, 16 orders, 26 families, 40 genera were identified and documented. Ciliate diversity was found to be highest in the water sample from Okhla bird sanctuary (OBS). All ciliate species recorded during the present study have been listed and their general characteristics have been discussed.

zoology↗

bioRxiv2020

Adaptation of pancreatic cancer cells to nutrient deprivation is reversible and requires glutamine synthetase stabilization by mTORC1

Pancreatic ductal adenocarcinoma (PDA) is a lethal, therapy-resistant cancer that thrives in a highly desmoplastic, nutrient-deprived microenvironment. Several studies investigated the effects of depriving PDA of either glucose or glutamine alone. However, the consequences on PDA growth and metabolism of limiting both preferred nutrients have remained largely unknown. Here, we report the selection for clonal human PDA cells that survive and adapt to limiting levels of both glucose and glutamine. We find that adapted clones exhibit increased growth in vitro and enhanced tumor-forming capacity in vivo. Mechanistically, adapted clones share common transcriptional and metabolic programs, including amino acid use for de novo glutamine and nucleotide synthesis. They also display enhanced mTORC1 activity that prevents the proteasomal degradation of glutamine synthetase (GS), the rate-limiting enzyme for glutamine synthesis. This phenotype is notably reversible, with PDA cells acquiring alterations in open chromatin upon adaptation. Silencing of GS suppresses the enhanced growth of adapted cells and mitigates tumor growth. These findings identify non-genetic adaptations to nutrient deprivation in PDA and highlight GS as a dependency that could be targeted therapeutically in pancreatic cancer patients. SignificancePancreatic ductal adenocarcinoma (PDA) is a highly lethal malignancy with no effective therapies. PDA aggressiveness partly stems from its ability to grow within a uniquely dense stroma restricting nutrient access. This study demonstrates that PDA clones that survive chronic nutrient deprivation acquire reversible non-genetic adaptations allowing them to switch between metabolic states optimal for growth under nutrient-replete or nutrient-deprived conditions. One contributing factor to this adaptation mTORC1 activation, which stabilizes glutamine synthetase (GS) necessary for glutamine generation in nutrient-deprived cancer cells. Our findings imply that although total GS levels may not be a prognostic marker for aggressive disease, GS inhibition is of high therapeutic value, as it targets specific cell clusters adapted to nutrient starvation, thus mitigating tumor growth.

cancer biology↗