Biology subjects

Begum, N.

Publications and source records attributed to Begum, N..

7 recordsLinked to original sources

bioRxiv2025

Enhanced Computational and Experimental Approaches for Comparative Analysis of the Human Mycobiome

The mycobiome is now recognized as a critical part of the human microbial ecosystem, playing a significant role in both health and disease. Mycobiome research is currently in its infancy and relies on fungal-specific primers with challenges in bioinformatics to accurately determine the structure of the mycobiota community. In addition, the majority of computational and experimental methods currently in use have been optimized for bacteria rather than for fungi. Here, we provide a comparative analysis of extraction methodologies for metagenome sequencing and subsequent bioinformatic analysis that will enhance fungal species identification. We utilized cultured mock fungal communities, including both yeast and mold species, to evaluate the efficiency of extraction protocols. We further enhanced computational analysis of the mycobiome, using mock and human metagenome data together with our curated catalogue consisting of 984 fungal genomes specific to the human mycobiome. Application of this optimised workflow for oral and gut samples of healthy individuals detected of novel species from Puccinia and Lentinus genera among the established presence of Malassezia, Rhizophagus, Candida and Saccharomyces genera. In addition, Enterocytozoon, was identified specifically in the gut mycobiome. Our pipeline enabled the comprehensive sampling of all fungal genes in a microbial community within a human sample minimising bias, reducing errors and artefacts from amplification, and providing accurate diversity and abundance data for the human mycobiome.

genomics↗

bioRxiv2025

Genome Sequencing, Molecular Marker Development and Genetic Diversity Assessment of Economically Important Vulnerable Tree Species Saraca asoca (Roxb.) W.J de Wilde

Saraca asoca, is an understory tree along streams in evergreen to semi-evergreen forests up to 600 m. It is an important tree in cultural tradition and medicinally significant. It is native to India and Sri Lanka. Globally the species is found to occur in India, Sri Lanka, Myanmar, Bangladesh. It was introduced in Malaysia. Within India, its found in Western Ghat and Eastern Ghat. It is occasionally planted in gardens. Saraca asoca is known for its extensive pharmacological properties, particularly its bark is used in treating menorrhagia, dysfunctional uterine bleeding, hemorrhagic dysentery, and other gynecological issues, it holds a prominent place in Ayurvedic medicine. This study was undertaken to sequence the whole genome of Saraca asoca using the Illumina HiSeq2500 platform, and evaluating the genetic diversity among samples from Kolluru and other locations in southern India through Genotyping by Sequencing (GBS). Analysis of 49 samples established genetic diversity relationships using a distance matrix. Sequencing yielded 1.6 Gb, covering 76% of the estimated genome size. The genome includes 764 million bases of repetitive DNA elements. A survey of Simple Sequence Repeats (SSRs) identified 584,615 SSRs, with 236,123 sequences containing SSRs. Utilizing the KEGG database, biosynthesis pathways for catechin and epicatechin within the flavonoid synthesis pathway were identified. This comprehensive genomic analysis of Saraca asoca (Sita Ashoka) provides critical insights for conservation efforts aimed at preserving this vulnerable species, Saraca asoca (Roxb.) Willd.

genomics↗

bioRxiv2024

Biallelic Loss of Molecular Chaperone Molecule AIP Results in a Novel Severe Multisystem Disease Defined by Defective Proteostasis

Children born with deleterious biallelic variants of the chaperone aryl hydrocarbon receptor interacting protein (AIP) have a novel pediatric metabolic disease presenting a severe, complex clinical phenotype characterized by failure to develop following birth. Analysis of Aip knockout mouse embryonic fibroblasts and patient-derived dermal fibroblasts revealed that AIP was required to support proteostasis; including proteasome activity, induction of autophagy and lysosome function. aip knockout zebrafish, recapitulated the phenotype of the children; dying at an early stage of development when autophagy is required to adapt to periods of starvation. Our results demonstrate that AIP plays a crucial role in initiating autophagy and maintaining proteostasis in vitro and in vivo. One Sentence SummaryHomozygous loss of the chaperone AIP results in a novel pediatric disease exhibiting multiple features of a lysosomal storage disease.

molecular biology↗

bioRxiv2023

Pathogenic entero- and salivatypes harbour changes in microbiome virulence and antimicrobial resistance genes with increasing chronic liver disease severity

Background & AimsLife-threatening complications of cirrhosis are triggered by bacterial infections, with the ever-increasing threat of antimicrobial resistance (AMR). Alterations in the gut microbiome in decompensated cirrhosis (DC) and acute-on-chronic liver failure (ACLF) are recognised to influence clinical outcomes, whilst the role of the oral microbiome is still being explored. Our aims were to simultaneously interrogate the gut and oral micro- and mycobiome in cirrhotic patients, and assess microbial community structure overlap in relation to clinical outcomes, as well as alterations in virulence factors and AMR genes. Methods18 healthy controls (HC), 20 stable cirrhotics (SC), 50 DC, 18 ACLF and 15 with non-liver sepsis (NLS) i.e. severe infection but without cirrhosis, were recruited at a tertiary liver centre. Shotgun metagenomic sequencing was undertaken from saliva (S) and faecal (F) samples (paired where possible). Salivatypes and enterotypes based on clustering of genera were calculated and compared in relation to cirrhosis severity and in relation to specific clinical parameters. Virulence and antimicrobial resistance genes (ARGs) were evaluated in both oral and gut niches, and distinct resistotypes identified. ResultsSpecific saliva- and enterotypes revealed a greater proportion of pathobionts with concomitant reduction in autochthonous genera with increasing cirrhosis severity, and in those with hyperammonemia. Overlap between oral and gut microbiome communities was observed and was significantly higher in DC and ACLF vs SC and HCs, independent of antimicrobial, beta-blocker and acid suppressant use. Two distinct gut microbiome clusters [ENT2/ENT3] harboured genes encoding for the phosphoenolpyruvate:sugar phosphotransferase system (PTS) system and other virulence factors in patients with DC and ACLF. Substantial numbers of ARGs (oral: 1,218 and gut: 672) were detected with 575 ARGs common to both sites. The cirrhosis resistome was significantly different to HCs, with three and four resistotypes identified for the oral and gut microbiome, respectively. DiscussionOral and gut microbiome profiles differ significantly with increasing severity of cirrhosis, with progressive dominance of pathobionts and loss of commensals. DC and ACLF have significantly worse microbial diversity than NLS, despite similar antimicrobial exposure, supporting the additive patho-biological effect of cirrhosis. The degree of microbial community overlap between sites, frequency of virulence factors and presence of ARGs, all increment significantly with hepatic decompensation. These alterations may predispose to higher infection risk, poorer response to antimicrobial therapy and worsening outcomes, and provide the rationale for developing non-antibiotic-dependent microbiome-modulating therapies.

physiology↗

bioRxiv2021

Biochemical characterization of a glycoside hydrolase family 43 β-D-galactofuranosidase from the fungus Aspergillus niger

{beta}-D-Galactofuranose (Galf) and its polysaccharides are found in bacteria, fungi and protozoa but do not occur in mammalian tissues, and thus represent a specific target for anti-pathogenic drugs. Understanding the enzymatic degradation of these polysaccharides is therefore of great interest, but the identity of fungal enzymes with exclusively galactofuranosidase activity has so far remained elusive. Here we describe the identification and characterization of a galactofuranosidase from the industrially important fungus Aspergillus niger. Phylogenetic analysis of glycoside hydrolase family 43 subfamily 34 (GH43_34) members revealed the occurrence of three distinct clusters and, by comparison with specificities of characterized bacterial members, suggested a basis for prediction of enzyme specificity. Using this rationale, in tandem with molecular docking, we identified a putative {beta}-D-galactofuranosidase from A. niger which was recombinantly expressed in Escherichia coli. The Galf-specific hydrolase, encoded by xynD demonstrates maximum activity at pH 5, 25 {degrees}C towards 4-Nitrophenyl-{beta}-galactofuranoside (pNP-{beta}-Galf), with a Km of 17.9 {+/-} 1.9 mM and Vmax of 70.6 {+/-} 5.3 mol min-1. The characterization of this first fungal GH43 galactofuranosidase offers further molecular insight into the degradation of Galf-containing structures and may inform clinical treatments against fungal pathogens.

biochemistry↗

bioRxiv2021

Integrative functional analysis uncovers metabolic differences between Candida species

Candida species are a dominant constituent of the human mycobiome and a better understanding of their metabolism from a fungal perspective can provide key insights into their ability to cause pathogenesis. Here, we have developed the BioFung database - a fungal specific tool for functional annotation using the KEGG database that provides an efficient method for annotation of protein-encoding gene. Analysis of carbohydrate-active enzyme (CAZymes) and BioFung, uncovered core and accessory features across Candida species demonstrating plasticity, adaptation to the environment and acquired features. Integerative functional analysis revealed that all Candida species can employ amino acid metabolism. However, metabolomics revealed that only a specific cluster of species (AGAu species - C. albicans, C. glabrata and C. auris) utilised amino acid metabolism. We identified critical metabolic pathways in the AGAu clusters with biomarkers and anti-fungal target potential in the CAZyme profile, polyamine, choline and fatty acid biosynthesis pathways. This study, combining genomic analysis, metabolomics and gene expression validation, highlights the metabolic diversity within AGAu species that underlies their remarkable ability to dominate the mycobiome and cause disease.

systems biology↗

bioRxiv2017

Epidemiological and ecological modelling reveal diversity in microbial population structures from a cross-sectional community swabbing study

Respiratory tract infections (RTI) are responsible for over 4 million deaths per year worldwide with pathobiont carriage a required precursor to infection. Through a cross-sectional community-based nasal self-swabbing study we sought to determine carriage epidemiology for respiratory pathogens amongst bacteria (Streptococcus pneumoniae, Haemophilus influenza, Moraxella catarrhalis, Staphylococcus aureus, Pseudomonas aeruginosa and Neisseria meningitidis) and viruses (RSV, Influenza viruses A and B, Rhinovirus/Enterovirus, Coronavirus, Parainfluenza viruses 1-3 and Adenovirus (ADV)). Carriage of bacterial and viral species was shown to vary with participant age, recent RTI and the presence of other species. The spatial structure of microbial respiratory communities was less nested (more disordered) in the young (0-4 years) and those with recent RTI. Species frequency distributions were flatter than random expectation in young individuals (X2 = 20.42, p = 0.002), indicating spatial clumping of species consistent with facilitative relationships amongst them. Deviations from a neutral model of ecological niches were observed for samples collected in the summer and from older individuals (those aged 5-17, 18-64 and [≥]65 years) but not in samples collected from winter, younger individuals (those aged 0-4 years), individuals with recent RTI and individuals without recent RTI, demonstrating the importance of both neutral and niche processes in respiratory community assembly. The application of epidemiological methods and ecological theory to sets of respiratory tract samples has yielded novel insights into the factors that drive microbial community composition, such as seasonality and age, as well as species patterns and interactions within the nose.

microbiology↗