Biology subjects

Behura, A.

Publications and source records attributed to Behura, A..

3 recordsLinked to original sources

bioRxiv2026

Co-occurring Amino Acid Substitutions Reveal Shared Evolutionary Links between Mammary Gland Location and Litter Size in Mammals

The mammary gland plays a critical role in mammalian development by producing milk to nourish offspring. The number and location of mammary glands vary among mammals. In humans and other primates that typically produce a single offspring, mammary glands are confined to the thoracic region. In contrast, litter bearing species possess mammary glands distributed along the milk line extending from the inguinal to the thoracic regions. In this study, we test the hypothesis that mammary gland location is evolutionarily linked to litter bearing capacity in mammals by performing large scale comparative and evolutionary analyses. We applied trait phylogeny Bayesian modeling to infer the coevolution of litter bearing capacity and mammary gland location (hereafter referred to as traits) and to assess the role of natural selection in shaping genes associated with this coevolution. To evaluate the functional relevance of the candidate genes, we conducted gene ontology and pathway enrichment analyses, inferred network and cluster patterns, and examined expression patterns in mammary glands and placentae. Additionally, we analyzed within species variation in protein sequences among pig breeds with low or high teat numbers and litter sizes to model the one half rule. Our results indicate that mammary gland location and litter bearing capacity are evolutionarily linked via site specific substitutions of amino acids, natural selection, and interconnected networks of a suite of proteins that are regulated in both mammary gland and placenta, and associated with specific biological functions including signal transduction, cell communication, and immune system function.

evolutionary biology↗

bioRxiv2025

Remote Host Manipulation by Pathogenic Bacterial Extracellular Vesicles

Bacterial extracellular vesicles (BEVs) are known to enhance infection susceptibility in vivo, yet the mechanistic basis for this remote preconditioning of host cells is unknown. Here, we discover an evolutionarily conserved, lipid-driven physical mechanism by which pathogenic bacterial EVs systemically arrest phagosome maturation in bystander host cells. Using live-cell fluorescence lifetime imaging, in vitro reconstitution and micromanipulation, we show that EVs from diverse pathogens - Mycobacterium tuberculosis, Klebsiella pneumoniae, and Staphylococcus aureus - fuse with host plasma, phagosomal, and lysosomal membranes. This fusion increase membrane order and perturbs early phagosomal maturation. Transcriptomic profiling confirms a broad downregulation of phagosome maturation genes while upregulation of lysosomal stress responsive genes. Crucially, in vitro reconstitution shows that EVs, and their purified lipids alone, are sufficient to induce phase separation and increase membrane order, directly inhibiting phago-lysosomal fusion. Our findings establish a paradigm in which pathogens exploit EVs not merely as delivery vehicles, but as tools to remotely rewire host cell membrane mechanics to hijack phagosome maturation and promote infection - a strategy that moves beyond canonical effector-based models of pathogenesis.

cell biology↗

bioRxiv2024

Real-time visualization reveals Mycobacterium tuberculosis ESAT-6 disrupts phagosome via fibril-mediated vesiculation

Mycobacterium tuberculosis (Mtb) evades host defense by hijacking and rupturing the phagosome, enabling it to escape to the host cytosol for its survival. ESAT-6, a secreted virulence protein of Mtb, is known to be critical for phagosome rupture. However, the mechanism of ESAT-6-mediated disruption of the phagosomal membrane remains unknown. Using in vitro reconstitution and numerical simulations, we discover that ESAT-6 polymerization remodels and vesiculates phagosomal membrane. In contrast to the pore formation triggered by a bilayer-spanning conformation, we find that the binding of ESAT-6 to the phagosomal membrane is shallow. Such shallow insertion leads to membrane shape transition leading to tubular and bud-like deformations on the membrane in a concentration-dependent manner, facilitated by the reduction in membrane tension and compressibility modulus. Strikingly, our observations suggest that ESAT-6 polymerizes in bulk and on the membrane, both in vitro and in macrophage. Numerical simulations demonstrate that growing fibrils generate both radial and tangential forces causing local remodeling and shape transition of the membrane. Using micropipette aspiration, we quantitatively show that ESAT-6 bound tensed membrane undergoes local changes in membrane curvature and lipid phase separation, also facilitated by the direct contact of the bacteria inside the phagosome. Nonetheless, the vesiculation of the buds is primarily driven by the forces exerted by the polymerization of ESAT-6. Such ESAT-6 mediated vesiculation induces apoptosis and host cell death in a concentration and time-dependent manner that promotes infection. Overall, the findings provide mechanistic insights into the long-standing question of phagosome disruption by Mtb for its escape.

biophysics↗