Biology subjects

M, A.

Publications and source records attributed to M, A..

5 recordsLinked to original sources

bioRxiv2025

Glycolysis-dependent Sulfur Metabolism Orchestrates Morphological Plasticity and Virulence in Fungi

Fungi exhibit remarkable morphological plasticity, which allows them to undergo reversible transitions between distinct cellular states in response to changes in their environment. This phenomenon, termed fungal morphogenesis, is critical for fungi to survive and colonize diverse ecological niches and establish infections in a variety of hosts. Despite significant advancements in the field with respect to understanding the gene regulatory networks that control these transitions, the metabolic determinants of fungal morphogenesis remain poorly characterized. In this study, we uncover a previously uncharacterized, conserved dependency between central carbon metabolism and de novo biosynthesis of sulfur-containing amino acids that is critical for fungal morphogenesis, in two key fungal species. Using a multidisciplinary approach, we demonstrate that glycolytic flux is crucial to drive fungal morphogenesis in a cAMP-independent manner and perturbation of this pathway leads to a significant downregulation in the expression of genes involved in de novo biosynthesis of sulfur-containing amino acids. Remarkably, exogenous supplementation of sulfur-containing amino acids robustly rescues the morphogenesis defect induced by the perturbation of glycolysis in both Saccharomyces cerevisiae and Candida albicans, underscoring the pivotal role of de novo biosynthesis of sulfur-containing amino acid as a downstream effector of morphogenesis. Furthermore, a C. albicans mutant lacking the glycolytic enzyme, phosphofructokinase-1 (Pfk1) exhibited significantly reduced survival within murine macrophages and attenuated virulence in a murine model of systemic candidiasis. Overall, our work elucidates a previously uncharacterized coupling between glycolysis and sulfur metabolism that is critical for driving fungal morphogenesis, contributing to our understanding of this conserved phenomenon.

microbiology↗

bioRxiv2025

Excitability and travelling waves in renewable active matter

Activity and renewability are distinctive features of living matter, and constitute a new class of materials that we term renewable active matter. A striking example is the cell cytoskeleton, where myosin filaments bind to the actin meshwork, apply contractile stresses and undergo continual stress/strain dependent turnover, thus acting as both force generators and sensors. As a consequence of nonreciprocity, arising from the independence of action and response, such living matter exhibits unusual mechanical properties like, segregation without attraction, fragility and force chains. Here we show that the interplay between activity and turnover gives rise to mechanical excitability in the form of travelling waves and pulses, and spatiotemporal chaos. We provide a systematic study of the nucleation, movement and shape of the travelling pulse, and present a boundary layer analysis to establish the existence of homoclinic orbits. Our analytical results are supported by detailed numerical analysis of the governing partial differential equations. This study has implications for the observed mechanical excitability in a variety of cellular contexts such as in isolated adherent cells and confluent cells within tissues.

biophysics↗

bioRxiv2025

Customized feminine hygiene wash containing postbiotics from Lactobacillus spp. to treat Urinary Tract Infections (UTI)

The rising prevalence of antimicrobial resistance has intensified the search for innovative therapeutic strategies, particularly in the prevention of urinary tract infections (UTIs). This study presents the development and evaluation of a novel postbiotics vaginal wash formulated to prevent UTIs by utilizing metabolites derived from indigenous vaginal Lactobacillus spp. The primary objective was to create a cost-effective, stable, and non-invasive solution targeting uropathogenic bacteria. Key metabolites, including tryptamine, (-)-terpinen-4-ol, and itaconic anhydride, were identified from cell free supernatant of vaginal Lactobacillus and incorporated into a poloxamer 407-based formulation. In vitro assays demonstrated significant bioactivity against uropathogenic bacteria, effectively inhibiting bacterial colonization and biofilm formation. Preclinical validation was conducted using BALB/c mice models to assess both the safety and efficacy of the vaginal wash. Results indicated a substantial reduction in infection rates among treated mice, with no observed adverse effects, confirming the formulations safety profile. In conclusion, this novel postbiotics vaginal wash represents a promising non-invasive therapeutic approach for UTI prevention. By harnessing bioactive metabolites from human vaginal Lactobacillus spp., the formulation offers a potential solution to combat antimicrobial resistance while improving womens health outcomes. Further clinical studies are warranted to validate these findings and explore broader applications in clinical practice, paving the way for new strategies in managing UTIs and enhancing overall female health.

microbiology↗

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↗

bioRxiv2023

Deletion of Xist upstream sequences alters TAD interactions and leads to defects in Xist coating and expression

The topological organization of the genome plays an important role in regulating gene expression. However, the connection between the two remains poorly understood. X-chromosome inactivation is a unique model system to explore the interlink between topologically associated domains (TADs) and gene expression. TADs are largely lost upon X-inactivation, and the inactive-X gets bipartitely reorganized into two large mega domains. However, the X-inactivation center (XIC) harbors two TADs - at the locus of long non-coding RNA Xist (Xist-TAD) and Tsix (Tsix-TAD). Xist is the master regulator of X-inactivation, which coat the inactive-X and facilitates heterochromatinization. Here, we deleted Xist upstream sequences ([~]6 kb) near the Xist TADs boundary in extraembryonic endoderm stem cells (XEN), which undergo imprinted X-inactivation. This deletion led to the major rearrangement of TADs and affected the expression of genes located within Xist and Tsix TAD, specially the expression of Xist was upregulated, suggesting TADs are essential for proper transcriptional regulation. On the other hand, Xist-upstream deletion on the inactive-X resulted in dispersal of Xist coating and loss of enrichment of repressive chromatin marks on the inactive-X but no effect on X-linked gene silencing. However, we found that autosomal genes were dysregulated in Xist-upstream deleted cells, probably because of misregulation of genes located in Xist and Tsix-TAD, specially Xist. We conclude that Xist upstream sequences are necessary for proper organization of the TADs at the XIC, maintenance of Xist coating/expression and autosomal gene expression.

genetics↗