Project description:The proline-rich antimicrobial peptide apidaecin (Api) inhibits bacterial protein synthesis in a distinctive way. In vitro biochemical and structural studies showed that Api binds in the nascent peptide exit tunnel of a ribosome that has completed translation of a gene and traps the release factors on the ribosome. By analyzing the distribution of ribosomes on mRNAs in Api-treated cells using Ribo-seq, we uncovered a range of effects that stem from the unique mechanism of Api action. Exposure of bacterial cells to Api results in arrest of ribosomes at stop codons, likely in a post-release state due to direct Api action, as well as in a pre-release state due to the depletion of available release factors. In addition, Api action leads to a pronounced queuing of translating ribosomes behind those arrested at stop codons. One of the major consequences of Api action is a dramatically increased level of stop codon bypass by ribosomes paused in a pre-release state, leading to an accumulation of proteins with C-terminal extensions, as confirmed by whole-cell proteomics analysis. Stop codon bypass occurs either in 0-frame, by misincorporation of a near-cognate aminoacyl-tRNA at the stop codon, or via frameshifting, allowing for a fraction of the translating ribosomes to reach the 3’ ends of mRNA transcripts. The pervasive stalling of pre-release ribosomes at the stop codons and at the RNA transcripts ends triggers activation of the cellular ribosome rescue systems which, likely due to Api action as well, remain ineffective. Understanding the unique mode of Api action as translation termination inhibitor in the cell can advance the development of treatments for infection and genetic diseases as well as new research tools for genome exploration.
Project description:Purpose: we searched for new potential druggable therapeutic targets through the description of high or low abundance transcripts that might be critical for ABC DLBCL cells.
Project description:This study demonstrates the usefulness of the API by generating a baseline gut microbiota profile of a healthy population and estimating reference intervals for the functional abundance of manually selected KEGG pathways. API facilitates microbiome research by providing dynamic and customizable tools for estimating reference intervals for gut microbiota functional abundances. Through the API, researchers can rapidly generate gut microbiota functional profiles of healthy populations to use as a baseline for comparison. The API also allows users to manually select specific KEGG pathways and estimate reference intervals for the functional abundance of those pathways. By generating these customized reference intervals, researchers can better understand the expected range of gut microbiota functions in healthy individuals. API enables microbiome studies to go beyond simple taxonomic profiling and delve deeper into the functional potential of gut microbiome communities. In summary, API represents a valuable tool for microbiome researchers that enhances the ability to elucidate connections between gut microbial functions and human health.
Project description:api mutant has been shown to be more resistant to P. palmivora than the A17 wild type (WT) line. In this study we want to compare both WT and mutant plant responses to the pathogen as well as their respective control transciptomes in order to identify api-dependent gene networks. Following germination, A17 or api plants grown in vitro on Agar medium were inoculated (or not = controls) with a P. palmivora zoospores (10^5/ml) and harvested 16 hours after inoculation. Three independent repeats were performed.
Project description:affy_infection_medicago - api mutant has been shown to be more resistant to P. palmivora than the A17 wild type (WT) line. In this study, we want to compare both WT and mutant plant responses to the pathogen as well as their respective control transcriptomes in order to identify api-dependent gene networks. Following germination, A17 or api plants grown in vitro on Agar medium were inoculated (or not = controls) with a P. palmivora zoospores (10^5/ml) and harvested 16 hours after inoculation. Three independent repeats were performed.
