Biology subjects

Fallman, M.

Publications and source records attributed to Fallman, M..

5 recordsLinked to original sources

bioRxiv2025

6S RNA facilitates bacterial virulence and adaptation at the epithelial barrier

Enteropathogenic bacteria must adapt dynamically to the complex gastrointestinal environment to successfully colonize host tissue and evade immune defenses. Using Yersinia pseudotuberculosis as a model, we performed in vivo spatial transcriptomics to investigate bacterial gene expression as it translocates from cecal lumen to associated lymphoid tissue in the mouse intestine. By optimizing bacterial RNA enrichment, we achieved near-complete transcriptome coverage and identified compartment-specific transcriptional profiles. Bacteria in lymphoid tissue exhibited elevated expression of virulence-associated type III secretion system (T3SS) genes and markers of increased replication, alongside a higher plasmid copy number. Oxygen availability emerged as an environmental cue for T3SS induction. Importantly, we discovered a role for the non-coding 6S RNA in accelerating virulence gene expression. Tissue-localized bacteria had significantly upregulated 6S RNA levels, and deletion of the ssrS gene encoding 6S RNA impaired T3SS gene expression and effector secretion. Further, spatial analyses of bacterial gene expression in foci of infected lymphoid tissue revealed heterogeneous expression patterns with significantly elevated expression of T3SS and 6S RNA in bacteria located close to surrounding phagocytes. Together these findings demonstrate that Y. pseudotuberculosis undergoes rapid transcriptional reprogramming upon epithelial barrier crossing coordinated by environmental sensing, where 6S RNA accelerates tissue colonization by promoting efficient expression of T3SS.

microbiology↗

bioRxiv2022

In vitro and in vivo infection models reveal connection between periplasmic protease Prc and alternative peptidoglycan synthase PBP3SAL in Salmonella enterica serovar Typhimurium

A hallmark in salmonellosis is the ability of the bacteria to proliferate within host cells. Most notably, Salmonella proliferates within professional phagocytes in a vacuolar compartment. During proliferation Salmonella has to build new cell wall, but how this is regulated within the intraphagosomal niche is not known. Here we show that genetically inactivating the periplasmic protease Prc, involved in cleaving peptidoglycan-processing enzymes, results in decreased fitness in macrophage-like RAW264.7 cells and in BALB/c mice, and in a decreased tolerance to redox stress. All these prc mutant phenotypes were conditional depending on pbp3sal, a recently defined paralogue for ftsl coding for the essential penicillin binding protein 3. These phenotypic connections between Prc and PBP3SAL adds to the phenotypes governed by Prc, and possibly adds PBP3SAL to the pool of target proteins involved in cell wall homeostasis that are regulated by Prc.

microbiology↗

bioRxiv2022

RpoN is required for a functional type III secretion system in Yersinia pseudotuberculosis

Pathogenic bacteria use a broad range of virulence factors to thrive within their host. Yersinia pseudotuberculosis, a gram-negative enteropathogen in humans, utilises a Type III secretion system to overcome the hosts innate immune response. A global regulator previously shown to be essential for virulence in Y. pseudotuberculosis is RpoN. We show here that a strain lacking RpoN has a severely reduced capacity to secrete Yop effectors. This strain has a substantially reduced expression of genes encoding structural components of the secretion apparatus, the ysc operons, while expression of genes encoding effectors and translocators is less affected. We show that RpoN regulates a complex network, where one part is suggested to contribute to inducing Type III secretion via the enhancer-binding protein GlrR/RpoN regulon. By analogy, during inducement of Type III secretion, RpoN has a positive effect on expression of the sigma factor RpoE, which also is known to act downstream of GlrR. Interestingly, we found putative RpoE binding sites upstream of the ysc operons, and also a partial rescue of Yop secretion in the rpoN mutant strain by overexpression of RpoE. Our findings suggest that the RpoN-mediated effect on expression of type III genes involves a sigma factor hierarchy, where RpoN via RpoE contributes to inducing Type III secretion.

molecular biology↗

bioRxiv2020

RNA Atlas of Human Bacterial Pathogens Uncovers Stress Dynamics Linked to Infection

Despite being genetically diverse, bacterial pathogens can adapt to similar stressful environments in human host, but how this diversity allows them to achive this is yet not fully understood. Knowledge gained through comparative genomics is insufficient as it lacks the level of gene expression reflecting gene usage. To fill this gap, we investigated the transcriptome of 32 diverse bacterial pathogens under 11 host related stress conditions. We revealed that diverse bacterial pathogens have common responses to similar stresses to a certain extent but mostly employ their unique repertoire with intersections between different stress responses. We also identified universal stress responders which shed light on the nature of antimicrobial targets. In addition, we found that known and unknown putative novel ncRNAs comprised a significant proportion of the responses. All the data is collected in PATHOgenex atlas, providing ample opportunities to discover novel players critical for virulence and maintenance of infection.

microbiology↗

bioRxiv2020

ProkSeq for complete analysis of RNA-seq data from prokaryotes

SummarySince its introduction, RNA-seq technology has been used extensively in studies of pathogenic bacteria to identify and quantify differences in gene expression across multiple samples from bacteria exposed to different conditions. With some exceptions, the current tools for assessing gene expression have been designed around the structures of eukaryotic genes. There are a few stand-alone tools designed for prokaryotes, and they require improvement. A well-defined pipeline for prokaryotes that includes all the necessary tools for quality control, determination of differential gene expression, downstream pathway analysis, and normalization of data collected in extreme biological conditions is still lacking. Here we describe ProkSeq, a user-friendly, fully automated RNA-seq data analysis pipeline designed for prokaryotes. ProkSeq provides a wide variety of options for analysing differential expression, normalizing expression data, and visualizing data and results, and it produces publication-quality figures. Availability and implementationProkSeq is implemented in Python and is published under the ISC open source license. The tool and a detailed user manual are hosted at Docker: https://hub.docker.com/repository/docker/snandids/prokseq-v2.1, Anaconda: https://anaconda.org/snandiDS/prokseq; Github: https://github.com/snandiDS/prokseq.

bioinformatics↗