Biology subjects

Fromion, V.

Publications and source records attributed to Fromion, V..

3 recordsLinked to original sources

bioRxiv2023

Comprehensive and Comparative Transcriptional Profiling of the Cell Wall Stress Response in Bacillus subtilis

The bacterial cell wall (CW) is an essential protective barrier and the frontline of cellular interactions with the environment and also a target for numerous antimicrobial agents. Accordingly, its integrity and homeostasis are closely monitored and rapid adaptive responses by transcriptional reprogramming induce appropriate counter-measures against perturbations. Here, we report a comprehensive and comparative transcriptional profiling of the primary cell envelope stress responses (CESR), based on combining RNAseq and high-resolution tiling array studies of the Gram-positive model bacterium Bacillus subtilis exposed to a range of antimicrobial compounds that interfere with cytoplasmic, membrane-coupled or extracellular steps of peptidoglycan (PG) biosynthesis. It revealed the complexity of the CESR of B. subtilis and unraveled the contribution of extracytoplasmic function sigma factors (ECFs) and two-component signal transduction systems (TCSs) to protect the cell envelope. While membrane-anchored steps are tightly controlled, early cytoplasmic and late extracellular steps of PG biosynthesis are hardly monitored at all. The ECF {sigma} factors {sigma}W and particularly {sigma}M provide a general CESR, while {sigma}V is almost exclusively induced by lysozyme, against which it provides specific resistance. Remarkably, {sigma}X was slightly repressed by most antibiotics, pointing towards a role in envelope homeostasis rather than CESR. It shares this role with the WalRK TCS, which balances CW growth with controlled autolysis. In contrast, all remaining TCSs are envelope stress-inducible systems. LiaRS is induced by a wide range of PG synthesis inhibitors, while the three paralogous systems BceAB, PsdRS and ApeRS are more compound-specific detoxification modules. Induction of the CssRS TCS by all antibiotics interfering with membrane-anchored steps of PG biosynthesis points towards a physiological link between CESR and secretion stress. Based on the expression signatures, a suite of CESR-specific B. subtilis whole cell biosensors were developed and carefully evaluated. This is the first comprehensive transcriptomic study focusing exclusively on the primary effects of envelope perturbances that shall provide a reference point for future studies on Gram-positive CESR.

microbiology↗

bioRxiv2019

RBA for eukaryotic cells: foundations and theoretical developments

Resource allocation models were recently identified as new ways to investigate cell design principles. In particular, the Resource Balance Analysis (RBA) framework is the first constraint-based modelling method capable of accurate quantitative predictions of the genome-wide resource allocation. Initially developed and validated on bacteria, the objective of this paper is to provide the mathematical fundations of the extension of the RBA framework to eukaryotic cells. We especially investigate the way to handle the cellular compartments in order to formalize eventually the functioning of organelles. It turns out that the final RBA problem for eukaryotic cells is close to the one of prokaryotic cells from a theoretical point of view. The mathematical properties that were already identified on the prokaryotic RBA framework can be easily transposed to eukaryotic cells. In particular, the eukaryotic RBA problem can be solved easily at the cell scale by Linear Programming. This paves the way to future developments of RBA models for eukaryotic cells.

systems biology↗

bioRxiv2019

Statistical modeling of bacterial promoter sequences for regulatory motif discovery with the help of transcriptome data: application to Listeria monocytogenes

Automatic de novo identification of the main regulons of a bacterium from genome and transcriptome data remains a challenge. To address this task, we propose a statistical model of promoter DNA sequences that can use information on exact positions of the transcription start sites and condition-dependent expression profiles. Two main novelties are to allow overlaps between motif occurrences and to incorporate covariates summarising expression profiles (e.g. coordinates in projection spaces or hierarchical clustering trees). All parameters are estimated using a dedicated trans-dimensional Markov chain Monte Carlo algorithm that adjusts, simultaneously, for many motifs and many expression covariates: the width and palindromic properties of the corresponding position-weight matrices, the number of parameters to describe position with respect to the transcription start site, and the choice of relevant expression covariates. A data-set of transcription start sites and expression profiles available for the Listeria monocytogenes is analysed. The results validate the approach and provide a new global view of the transcription regulatory network of this important model food-borne pathogen. A previously unreported motif that may play an important role in the regulation of growth was found in promoter regions of ribosomal protein genes.

bioinformatics↗