Biology subjects

Pareek, A.

Publications and source records attributed to Pareek, A..

3 recordsLinked to original sources

bioRxiv2023

SWI/SNF complex-mediated chromatin remodelling is vital for cell surface adhesin repression and immune evasion

Immune evasion is critical for fungal virulence. However, how the human opportunistic pathogen Candida glabrata (Cg) accomplishes this is unknown. Here, using micrococcal nuclease-sequencing, RNA-sequencing, macrophage-signalling and genetic analyses, we demonstrate that chromatin reorganization in macrophage-internalized Cg, via CgSnf2 (ATPase subunit of the SWI/SNF chromatin remodelling complex), leads to upregulation and downregulation of immunosuppressive seven mannosyltransferase-cluster (CgMT-C) and immunostimulatory cell surface adhesin EPA1 genes, respectively. Consistently, EPA1 overexpression and CgMT-C deletion led to increased IL-1{beta} (pro-inflammatory cytokine) production and reduced Cg proliferation in macrophages. Further, CgSNF2 deletion evoked increased IL-1{beta} secretion, and the consequent killing of macrophage-internalized Cg, with elevated IL-1{beta} levels being partially reversed in Akt-, p38-, NF-{kappa}B- or NLRP3 inflammasome-inhibited macrophages. Importantly, macrophages respond to multiple Candida pathogens via NF-{kappa}B-dependent IL-1{beta} production, underscoring NF-{kappa}B signallings role in fungal diseases. Finally, we present the first genome-wide nucleosome map of macrophage-internalized Cg consisting of [~]12,000 dynamic and 70,000 total nucleosomes. Altogether, our findings directly link the nucleosome positioning-based chromatin remodelling to fungal immunomodulatory molecule expression, which dictates Cg fate in host immune cells.

microbiology↗

bioRxiv2022

Targeting host protein G3BP1 for the discovery of novel antiviral inhibitors against the Chikungunya virus

Molecular interactions of Chikungunya virus (CHIKV) nsP3 with the host G3BP1 stress granule (SG) protein is crucial for CHIKV replication. NsP3 binds to the nuclear transport factor 2 (NTF2)-like domain of G3BP1 via its two FGDF motifs, unsettling SGs formation. The present study identified seven small molecules targeting the FGDF binding pocket of G3BP1 using structure-based computer-aided drug discovery. All seven molecules exhibited good binding affinities in the range of [~]3.4 to [~]98M towards NTF2-like G3BP1 domain. Furthermore, identified molecules demonstrate dose-dependent inhibition in CHIKV infected Vero cells (EC50: 0.40 to 7.39{micro}M), and reduced SGs formation in these cells. These results highlight G3BP1 protein as a potential CHIKV therapeutic target and offer potential prospective for developing treatment for CHIKV disease.

microbiology↗

bioRxiv2021

Effects of sub-lethal single, simultaneous, and sequential abiotic stresses on phenotypic traits of Arabidopsis thaliana

Plant responses to abiotic stresses are complex and dynamic, and involve changes in different traits, either as the direct consequence of the stress, or as an active acclimatory response. Abiotic stresses frequently occur simultaneously or in succession, rather than in isolation. Despite this, most studies have focused on a single stress and single or few plant traits. To address this gap, our study comprehensively and categorically quantified the individual and combined effects of three major abiotic stresses associated with climate change (flooding, progressive drought and high temperature) on 12 phenotypic traits related to morphology, development, growth and fitness, at different developmental stages in four Arabidopsis thaliana accessions. Combined sub-lethal stresses were applied either simultaneously (high temperature and drought) or sequentially (flooding followed by drought). In total, we analyzed the phenotypic responses of 1782 individuals across these stresses and different developmental stages. Overall, abiotic stresses and their combinations resulted in distinct patterns of effects across the traits analyzed, with both quantitative and qualitative differences across accessions. Stress combinations had additive effects on some traits, whereas clear positive and negative interactions were observed for other traits: 9 out of 12 traits for high temperature and drought, 6 out of 12 traits for post-submergence and drought showed significant interactions. In many cases where the stresses interacted, the strength of interactions varied across accessions. Hence, our results indicated a general pattern of response in most phenotypic traits to the different stresses and stress combinations, but it also indicated a natural genetic variation in the strength of these responses. Overall, our study provides a rich characterization of trait responses of Arabidopsis plants to sub-lethal abiotic stresses at the phenotypic level and can serve as starting point for further in-depth physiological research and plant modelling efforts.

plant biology↗