Biology subjects

Borbora, S. M.

Publications and source records attributed to Borbora, S. M..

4 recordsLinked to original sources

bioRxiv2026

Tissue osmotic surveillance shapes susceptibility of zebrafish to wound infections

Wounds represent compromised tissues that are susceptible to opportunistic infections. Tissue factors predisposing to wound infection include edema, poor vascularity, tissue hypoxia, necrosis, and wound size. However, it is unclear whether factors external to the tissue play a role. Detection of osmolarity imbalances between internal and external environment has been shown to alter epithelial wound closure and immune cell recruitment at injury sites. However, it remains unclear whether these osmotic surveillance pathways affect susceptibility to pathogenic wound infections. Here, we use live imaging and disease monitoring in zebrafish larvae to understand susceptibility of wound infection towards Pseudomonas aeruginosa. We show that exposure of wounds to isotonic solution results in enhanced susceptibility and pathogen burden. Furthermore, we demonstrate that this higher propensity for infection depends on osmolarity-mediated changes in wound sealing and neutrophil recruitment during the early stages of the wound response. These findings inform the design of experimental wound infection models as well as the clinical management of wounds.

cell biology↗

bioRxiv2025

In form for a swarm: programmable neutrophil swarming impacts infection outcome

Many migrating cells pattern signalling molecules to support their accumulation in target tissues. During inflammation, neutrophils achieve rapid swarming at sites of injury or infection by generating spatiotemporal gradients of chemoattractants. Whether these self-generated behaviours can be re-programmed to change disease course is unclear. Here, we show that neutrophil chemoattractant patterning machinery is subject to transcriptional reprogramming after microbial experience, leading to enhanced swarming and control of infection at subsequent wound sites in zebrafish. Through in vitro assays, we demonstrate that "trained swarming phenotypes" are cell-intrinsic and independent of the nature of the microbial target. Furthermore, genetic enhancement of 5-lipoxygenase in neutrophils is sufficient to improve neutrophil swarming and resistance to wound infection. Through mathematical modelling, we demonstrate that neutrophil-intrinsic alterations in chemoattractant release are sufficient to recapitulate trained swarming in infection-experienced animals. Together, these data suggest new routes for reprogramming cell migration in disease settings, via manipulating their ability to shape chemoattractant landscapes.

immunology↗

bioRxiv2022

Mycobacterium tuberculosis infection elevates SLIT2 expression to modulate oxidative stress responses in macrophages

Mycobacterium tuberculosis (Mtb), the causative agent of the pulmonary ailment, tuberculosis (TB), continues to thrive owing to a disorganized immune response against it by the host. Among other factors, the rewiring of distinct host signaling pathways is effectuated by the intracellular bacterium, resulting in pathogen-favorable outcomes. Oxidative stress build-up is a key cellular manifestation that occurs during mycobacterial infection. Enhanced oxidative stress is brought about by the cumulative effect of elevated reactive oxygen species generation as well as the inept ability of the cell to mitigate ROS levels. Here, we report the increased expression of the neuronal ligand, SLIT2, during mycobacterial infection in macrophages. By employing loss of function analysis using specific inhibitors, we attribute the heightened expression of SLIT2 to the Mtb-mediated phosphorylation of the p38/JNK pathways. Also, using chromatin immunoprecipitation (ChIP) analysis, we found reduced levels of the repressive H3K27me3 signature on the Slit2 promoter during mycobacterial infection. Furthermore, SLIT2 was found to promote the expression of cellular pantetheinase, Vanin1 (VNN1), that contributed to copious levels of ROS within the macrophage cellular milieu. Thus, we dissect essential molecular details leading to the robust expression of SLIT2 during Mtb infection while outlining the potential consequences of SLIT2 upregulation in infected macrophages. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/512188v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@352ec6org.highwire.dtl.DTLVardef@19209e5org.highwire.dtl.DTLVardef@c7c546org.highwire.dtl.DTLVardef@168ab61_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2021

PRMT5 epigenetically regulates the E3 ubiquitin ligase ITCH to influence lipid accumulation during mycobacterial infection

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), triggers enhanced accumulation of lipids to generate foamy macrophages (FMs). This process has been often attributed to the surge in the expression of lipid influx genes with a concomitant decrease in those involved in lipid efflux genes. Here, we define an Mtb-orchestrated modulation of the ubiquitination mechanism of lipid accumulation markers to enhance lipid accretion during infection. We find that Mtb infection represses the expression of the E3 ubiquitin ligase, ITCH, resulting in the sustenance of key lipid accrual molecules viz. ADRP and CD36, that are otherwise targeted by ITCH for proteasomal degradation. In line, overexpressing ITCH in Mtb-infected cells was found to suppress Mtb-induced lipid accumulation. Molecular analyses including loss-of-function and ChIP assays demonstrated a role for the concerted action of the transcription factor YY1 and the arginine methyl transferase PRMT5 in restricting the expression of Itch gene by conferring repressive symmetrical H4R3me2 marks on its promoter. Consequently, siRNA-mediated depletion of YY1 or PRMT5 rescued ITCH expression, thereby compromising the levels of Mtb-induced ADRP and CD36 and limiting FM formation during infection. Accumulation of lipids within the host has been implicated as a pro-mycobacterial process that aids in pathogen persistence and dormancy. In our study, perturbation of PRMT5 enzyme activity resulted in compromised lipid levels and reduced mycobacterial survival in primary murine macrophages (ex vivo) and in a therapeutic mouse model of TB infection (in vivo). These findings provide new insights on the role of PRMT5 and YY1 in augmenting mycobacterial pathogenesis. Thus, we posit that our observations could help design novel adjunct therapies and combinatorial drug regimen for effective anti-TB strategies. Author SummaryMycobacterium tuberculosis generates lipid-laden cells (foamy macrophages-FMs) that offer a favorable shelter for its persistence. During infection, we observe a significant reduction in the expression of the E3 ubiquitin ligase, ITCH. This repression allows the sustenance of key lipid accretion molecules (ADRP and CD36), by curbing their proteasomal degradation. Further, we show the repression of ITCH to be dependent on the concerted action of the bifunctional transcription factor, YY1 and the arginine methyl transferase, PRMT5. NOTCH signaling pathway was identified as a master-regulator of YY1 expression. In vitro and in vivo analyses revealed the significance of PRMT5 in regulating FM formation and consequently mycobacterial burden.

microbiology↗