Biology subjects

Antani, J. D.

Publications and source records attributed to Antani, J. D..

6 recordsLinked to original sources

bioRxiv2026

SUN2 mediates epigenetic remodeling to drive mechanotransduction during skin fibrosis

Fibrosis involves sustained changes in fibroblast gene expression, leading to excessive extracellular matrix (ECM) deposition and progressive tissue stiffening. Although matrix stiffness is a potent regulator of cell fate and transcription, it is not clear how nuclear mechanosensing contributes to fibrosis. Here, we define a central role for SUN2, a component of linker of nucleoskeleton and cytoskeleton (LINC) complexes, as a mediator of stiffness-dependent nuclear and chromatin responses during skin fibrosis. SUN2 transcripts are upregulated in dermal fibroblasts of patients with systemic sclerosis and Sun2 protein is elevated in fibrotic mouse skin. Nuclear size, A-type lamins and Sun2 are elevated in dermal fibroblasts plated on stiff substrates. Loss of Sun2 protects against bleomycin-induced skin fibrosis in vivo and abolishes stiffness-induced changes in nuclear size and fibrotic gene expression in vitro. Mechanistically, we identify three Sun2-dependent mechanosensitive chromatin states and show that mechanical induction of the histone methyltransferase Ezh2 requires Sun2. These findings define SUN2 as a nuclear mechanosensor that couples matrix stiffness to chromatin regulation and transcriptional programs that drive fibrosis, identifying it as a potential therapeutic target pathway in fibrotic disease.

cell biology↗

bioRxiv2026

Prophage activity shapes the thermal ecology and evolution of a marine bacterial host

Predicting the response of populations to thermal change is challenging due to temperature-dependent interspecific interactions, such as those between bacteria and their integrated viruses (prophages). Temperature is known to modulate prophage activity, raising the question of whether and how prophages alter host responses to temperature. In this work, we explored how prophage infection shapes host thermal ecology and evolution in a novel marine bacterial isolate carrying a spontaneously inducing prophage. We first characterized the effect of temperature on bacteria and phage population dynamics, finding that high temperatures led to bacterial population crashes and reduced yield, with abundant phage production across all temperatures. To then determine the causal impacts of this phage, we infected a conspecific susceptible strain and found that performance in the novel lysogen was reduced across all temperatures and indistinguishable from the naturally infected strain. Further, we found that evolutionary rescue mutants of the naturally infected strain with an expanded upper thermal limit gained high temperature adaptation through a reduction in prophage activity. Overall, we found that intraspecific variation in thermal ecology was explained by prophage infection, and that adaptation to nonpermissive temperature occurred through modifications to prophage dynamics. This work demonstrates a critical link between viral mobile genetic elements and bacterial thermal responses, and emphasizes the importance of ecological interactions in thermal ecology and evolution.

ecology↗

bioRxiv2025

Evolutionary consequences of bacterial resistance to a flagellotropic phage

Bacteria can evolve resistance to bacteriophage attack via mutations that alter phage receptors on the cell surface. Flagellotropic phages bind to motility-enabling flagella, creating an evolutionary trade-off, since losing flagellar function reduces fitness in many environments. We experimentally evolved Escherichia coli populations under selection by flagellotropic phage (chi), on soft-agar swim plates which favor motility. Whole genome sequencing revealed early emergence of non-motile mutants with disrupted motility-genes, followed by motile mutants with flagellin gene mutations. Swim-plate assays and single-cell tracking showed variable motility effects among resistant mutants, with some faster and others slower than ancestors. Increased tumble bias suggested altered flagellar rotation. Kinase-response in the upstream chemotaxis pathway was also remodeled in -resistant mutants. Our findings demonstrate that evolved phage-resistance can cause motility to trade-off or trade-up, revealing diverse evolutionary outcomes under combined selection pressures. TeaserEvolution redesigns bacterial swimming and navigation to escape viruses while maintaining motility in complex environments.

evolutionary biology↗

bioRxiv2024

Identification of a large cohort of Enterobacter jumbo phages with broad host ranges across pathogenic Gammaproteobacteria

ESKAPE pathogens cause most hospital-acquired infections globally and often carry antibiotic resistance. Many of them have been the target of bacteriophage therapies. Enterobacter is an ESKAPE pathogen but is less frequently a target for phage therapy due to a relative lack of available phages. We isolated eight jumbo phages with genomes ranging from 223 to 366 kbp targeting Enterobacter spp. and found that they belonged to separate phage clades. Six of them formed nucleus-like structures confirmed by DAPI-staining, and were phylogenetically related to Chimalliviridae. Two jumbo phages did not form nucleus-like structures and did not cluster with Chimalliviridae. Although these jumbo phages were found on Enterobacter, many were closely related to phages with non-Enterobacter hosts. To test whether these phages may have had expanded host ranges, we examined 14 pathogenic Gammaproteobacteria and found that these phages were capable of creating plaques on 8 of them. These species included Escherichia coli, Klebsiella aerogenes, Serratia marcescens, Salmonella spp., Shigella spp., Providencia spp., Citrobacter spp., and Cronobacter sakazakii. We verified that there was phage amplification in these microbes rather than lysis from without by performing qPCR to confirm DNA replication in each species. Phages typically have narrow host ranges, a benefit for microbiome-sparing compared to antibiotics. However, the broad host ranges of these Gammaproteobacteria jumbo phages suggests that not all phages have the same risk/benefit ratios. While this broad range could aid their development as antibiotic alternatives, further study is needed to assess potential microbiome disruption. SignificanceWith the growing threat of antibiotic resistant bacteria, alternative treatments like bacteriophages have emerged. Bacteriophages typically have narrow host ranges, a disadvantage compared to antibiotics. We discovered eight jumbo phages that kill antibiotic resistant Enterobacter, but were diverse phylogenetically. Six of them formed nucleus-like structures and were members of the Chimalliviridae family and the other two did not form nucleus-like structures. We confirmed that each phage had broad host ranges capable of lysing at least eight different human Gammaproteobacteria including pathogens such as E. coli, K. aerogenes, and S. marcescens. By identifying broad host range jumbo phages that attack pathogens, we may have identified phages with spectrums of activity more similar to antibiotics than have been traditionally attributed to phages.

microbiology↗

bioRxiv2024

Microscopic Phage Adsorption Assay: High-throughput quantification of virus particle attachment to host bacterial cells

Phages, viruses of bacteria, play a pivotal role in Earths biosphere and hold great promise as therapeutic and diagnostic tools in combating infectious diseases. Attachment of phages to bacterial cells is a crucial initial step of the interaction. The classic assay to quantify the dynamics of phage attachment involves co-culturing and enumeration of bacteria and phages, which is laborious, lengthy, hence low-throughput, and only provides ensemble estimates of model-based adsorption rate constants. Here, we utilized fluorescence microscopy and particle tracking to obtain trajectories of individual virus particles interacting with cells. The trajectory durations quantified the heterogeneity in dwell time, the time that each phage spends interacting with a bacterium. The average dwell time strongly correlated with the classically-measured adsorption rate constant. We successfully applied this technique to quantify host-attachment dynamics of several phages including those targeting key bacterial pathogens. This approach should benefit the field of phage biology by providing highly quantitative, model-free readouts at single-virus resolution, helping to uncover single-virus phenomena missed by traditional measurements. Owing to significant reduction in manual effort, our method should enable rapid, high-throughput screening of a phage library against a target bacterial strain for applications such as therapy or diagnosis.

microbiology↗

bioRxiv2022

Lamin A/C mediated invaginations in the nuclear surface allow the nucleus to pass unimpeded through a dense array of fiber-like obstacles

Migrating cells must deform their stiff cell nucleus to move through pores and fibers in tissue. Lamin A/C is known to hinder cell migration by limiting nuclear deformation and passage through confining channels, but its role in nuclear deformation and passage through fibrous environments is less clear. We studied cell and nuclear migration through discrete, closely spaced, slender obstacles which mimic the mechanical properties of collagen fibers. Nuclei bypassed slender obstacles while preserving their overall morphology by deforming around them with deep local invaginations of little resisting force. The obstacles did not impede the nuclear trajectory or cause a rupture of the nuclear envelope. Nuclei likewise deformed around single collagen fibers in cells migrating in 3D collagen gels. In contrast to its limiting role in nuclear passage through confining channels, lamin A/C facilitated nuclear deformation and passage through fibrous environments; nuclei in lamin-null (Lmna-/-) cells lost their overall morphology and became entangled on the obstacles. Analogous to surface tension-mediated deformation of a liquid drop, lamin A/C imparts a surface tension on the nucleus that allows nuclear invaginations with little mechanical resistance, preventing nuclear entanglement and allowing nuclear passage through fibrous environments.

cell biology↗