Biology subjects

Biswas, C.

Publications and source records attributed to Biswas, C..

4 recordsLinked to original sources

bioRxiv2023

Transcription Factor NRF2 is Activated by Erythrophagocytosis of Oxidized Red Blood Cell Products and Suppresses the IL-12-IFNg-IL-10 Axis in a Murine Model of Hyperinflammatory Disease

Hyperinflammatory diseases including macrophage activation syndrome (MAS) and hemophagocytic lymphohistocytosis (HLH) are characterized by multi-lineage cytopenias, hypercytokinemia, and tissue hemophagocytosis. However, the mechanisms by which erythrophagocytosis mediates iron metabolism and regulates the hyperactive immune response remain unclear. The transcription factor NRF2 is an important sensor for inflammatory and redox distress. The targets of NRF2 are antioxidant response elements responsible for transcription of genes related to restoration of redox homeostasis within the cell. Here we demonstrate that mice with CpG-induced MAS have evidence of systemic oxidative and nitrosative distress - including increased serum nitric oxide and elevated systemic lipid peroxidation. In this model, NRF2 knockout mice develop significantly worse organomegaly, hypercytokinemia, and reticulocytosis. NRF2 knockout mice have unexpected exacerbation in the cytokines that are central to hyperinflammatory physiology - namely IL-12, IFN gamma (IFNg), and IL-10. In vitro we demonstrate that oxidized red blood cell products and heme itself suppress IL-12 protein production and transcription from bone marrow derived dendritic cells in a NRF2-dependent manner. Together our studies demonstrate that erythrophagocytosis of oxidized red blood cell products suppresses the Il-12-IFNg-IL-10 axis which drives hyperinflammation in murine hyperinflammation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/571271v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1a2330corg.highwire.dtl.DTLVardef@1c59944org.highwire.dtl.DTLVardef@1d151b5org.highwire.dtl.DTLVardef@14b4301_HPS_FORMAT_FIGEXP M_FIG C_FIG Created with BioRender

immunology↗

bioRxiv2019

Prevention of enteric bacterial infections and modulation of gut microbiota composition with conjugated linoleic acids producing Lactobacillus in mice

Probiotics are recognized to outcompete pathogenic bacteria by receptor-mediated colonizing and secreting functional metabolites which have direct antimicrobial activities towards pathogens and/or improving hosts gut health and immunity. We have constructed a Lactobacillus casei (LC) probiotic strain, LC+mcra, by inserting mcra (myosin cross-reactive antigen) gene, which stimulates the conversion of conjugated linoleic acids. In this study, we evaluated the protective roles of LC+mcra against pathogenic Salmonella enterica serovar Typhimurium (ST) and enterohaemorrhagic E. coli (EHEC) infection in BALB/cJ mice. Through a series of in vivo investigation, we observed that LC+mcra colonized efficiently in mice gut and competitively reduced the infection with ST and EHEC in various locations of small and large intestine, specifically cecum, jejunum, and ileum (p<0.05). The cecal microbiota in ST-challenged mice with LC+mcra protection were positively modulated with higher relative abundances Firmicutes but lower Proteobacteria plus increased bacterial species diversity/richness based on 16S metagenomic sequencing. Based on cytokine gene expression analysis by qRT-PCR, mice pretreated with LC+mcra were found with attenuated bacterial pathogen-induced gut inflammation. Furthermore, mice fed LC+mcra daily for one week could protect themselves from the impairments caused by enteric infections with ST or EHEC. These impairments include weight loss, negative hematological changes, intestinal histological alterations, and potential death. This in vivo study suggests that daily consumption of novel conjugated linoleic acids over-producing probiotic might be efficient in improving gut intestinal microbiome composition and preventing/combating foodborne enteric bacterial infections with pathogenic Salmonella and diarrheagenic E. coli.\n\nAuthor summaryNumerous bacteria colonize throughout the gastrointestinal tract and form a complex microbial ecosystem known as gut microbiota. A balanced microbial composition is crucial for maintaining proper gut health and host defense against pathogenic microbes. However, enteric bacterial infections could cause illness and even lead to death of host when foodborne pathogens like Salmonella and enterohaemorrhagic E. coli (EHEC) invade gut intestine and cause imbalance of gut microbiota. Beneficial microbes in gastrointestinal tract such as Lactobacillus and their secreted bio-active metabolites, are potential bio-agents to improve gut immunity and outcompete bacterial pathogens. In this study, to evaluate roles of novel Lactobacillus strain LC+mcra which produce higher amount of a group of beneficial secondary metabolites called conjugated linoleic acids, we have shown that daily oral administration of this LC+mcra for one-week in mice lead to higher proportion of beneficial bacterial colonization in different locations of intestine and a significant reduction of pathogenic Salmonella and EHEC colonization. Furthermore, mice fed with LC+mcra restore and modulate Salmonella infection-induced negative impact on gut microbiota composition and protect themselves from various levels of physiological damage.

microbiology↗

bioRxiv2018

Cryo-EM structures reveal dynamic interplay of nascent chain-processing factors on the ribosome

During protein biosynthesis in bacteria, one of the earliest phenomena that a nascent polypeptide chain experiences is the co-translational enzymatic processing. The event includes two enzymatic pathways, deformylation of the N-terminal methionine followed by methionine excision catalyzed by peptide deformylase (PDF) and methionine aminopeptidase (MetAP). The ribosome tunnel exit serves as the podium for recruiting proteins involved in maturation processes of the nascent chain. During the process, the emerging nascent protein likely remains shielded by the chaperone trigger factor (TF).\n\nHere, we present the first cryo-EM structures of E. coli ribosome in complex with the nascent chain processing proteins. The structures reveal overlapping binding sites for PDF and MetAP when they bind individually at the tunnel exit site, where proteins L22 and L32 are identified as primary anchoring sites for both proteins. Interestingly however, MetAP has a remarkable ability of repositioning itself to adjacent locations in the presence of PDF and TF at the tunnel exit. Thus, our results disclose an unexpected scanning mechanism that MetAP adopts for context-specific ribosome association.

biochemistry↗

bioRxiv2017

Electron microscopy reveals unique nano forms of bacterial spores

Endospore formation under environmental stress conditions is a well-established phenomenon for members of bacterial phylum Firmicutes, among which the most well studied ones belong to genus Bacillus and Clostridium. So far, known sizes of the spores are all larger than 500 nm. Nano-forms of bacteria have been reported but the notion still remains controversial. In this study, we provide visual evidences of living nano-entities (named here as nano-spores) formed by a bacterial species Bacillus cereus under prolonged stress, which are capable of escaping though standard sterile filtration procedure. The existence of nano-forms of bacteria was initially identified in a yeast ribosome preparation. We further demonstrate the transformation of the nano-spores into mature cells upon nutrient supply. Our study not only demonstrates the ability of bacteria to get transformed into yet-unknown form in order to survive under harsh environment, but also brings to light the existence of the smallest possible form of life.

microbiology↗