A5071212554- Salmonella and Campylobacter epidemiology
- Escherichia coli research studies
- Vibrio bacteria research studies
- Inflammasome and immune disorders
- Viral gastroenteritis research and epidemiology
- Immune Response and Inflammation
- Gut microbiota and health
- Bacteriophages and microbial interactions
- Food Allergy and Anaphylaxis Research
- Microtubule and mitosis dynamics
- IL-33, ST2, and ILC Pathways
- Mast cells and histamine
- Amoebic Infections and Treatments
- Cancer Research and Treatments
- Parasites and Host Interactions
- Cancer Cells and Metastasis
- Cellular Mechanics and Interactions
- Fungal and yeast genetics research
- Digestive system and related health
- Bacterial biofilms and quorum sensing
- Bacterial Genetics and Biotechnology
- Clostridium difficile and Clostridium perfringens research
- Parasitic Infections and Diagnostics
- Genomics and Chromatin Dynamics
- Genetic Neurodegenerative Diseases
Science for Life Laboratory
2017-2024
Uppsala University
2016-2024
ETH Zurich
2012-2021
Czech Academy of Sciences, Institute of Microbiology
2020
Umeå University
2007-2014
Board of the Swiss Federal Institutes of Technology
2014
St. Jude Children's Research Hospital
2011
Septins are conserved GTP-binding proteins that assemble into lateral diffusion barriers and molecular scaffolds. Vertebrate genomes contain 9-17 septin genes encode both ubiquitous tissue-specific septins. Expressed septins may in various combinations through heterotypic homotypic G-domain interactions. However, little is known regarding assembly states of mammalian mechanisms directing ordered individual heteromeric units, which the focus this study. Our analysis system cells lacking or...
Bacteriophage transfer (lysogenic conversion) promotes bacterial virulence evolution. There is limited understanding of the factors that determine lysogenic conversion dynamics within infected hosts. A murine Salmonella Typhimurium (STm) diarrhea model was used to study SopEΦ, a prophage from STm SL1344, ATCC14028S. Gut inflammation and enteric disease triggered >55% ATCC14028S 3 days. Without inflammation, SopEΦ reduced by up 105-fold. This because (e.g., reactive oxygen species, nitrogen...
•Live imaging of Salmonella near-surface swimming on mouse colon inner mucus layer•Colon layer traversal requires breaches and flagellar propulsion•The cecum lacks a continuous layer, leaving epithelium tips uncovered•Exposed are hotspot for infection SummaryMucus separates gut-luminal microbes from the tissue. It is unclear how pathogens like Typhimurium (S.Tm) can overcome this obstacle. Using live microscopy, we monitored S.Tm interactions with native murine gut explants studied affects...
Inflammasomes can prevent systemic dissemination of enteropathogenic bacteria. As adapted pathogens including Salmonella Typhimurium (S. Tm) have evolved evasion strategies, it has remained unclear when and where inflammasomes restrict their dissemination. Bacterial population dynamics establish that the NAIP/NLRC4 inflammasome specifically restricts S. Tm migration from gut to draining lymph nodes. This is solely attributable within intestinal epithelial cells (IECs), while evades...
FinO domain proteins such as ProQ of the model pathogen Salmonella enterica have emerged a new class major RNA-binding in bacteria. has been shown to target hundreds transcripts, including mRNAs from many virulence regions, but its role, if any, bacterial pathogenesis not studied. Here, using Dual RNA-seq approach profile ProQ-dependent gene expression changes infects human cells, we reveal dysregulation motility, chemotaxis, and genes which is accompanied by altered MAPK (mitogen-activated...
The gut epithelium is a critical protective barrier. Its NAIP/NLRC4 inflammasome senses infection by Gram-negative bacteria, including Salmonella Typhimurium (S.Tm) and promotes expulsion of infected enterocytes. During the first ~12-24 h, this reduces mucosal S.Tm loads at price moderate enteropathy. It remained unknown how NAIP/NLRC4-dependent tradeoff would develop during subsequent stages. In NAIP/NLRC4-deficient mice, elicited severe enteropathy within 72 characterized elevated TNF (>20...
Topological, chemical and immunological barriers are thought to limit infection by enteropathogenic bacteria. However, in many cases these their consequences for the process remain incompletely understood. Here, we employed a mouse model Salmonella colitis mixed inoculum approach identify limiting gut luminal pathogen population. Mice were infected via oral route with wild type S. Typhimurium (S. Tm) and/or mixtures of phenotypically identical but differentially tagged Tm strains (“WITS”,...
Significance Contractile movements in the mammalian intestine typically rely on dedicated muscle cells. Here, we however show that untransformed intestinal epithelial cell layers initiate immediate focal contractions, affecting hundreds to thousands of cells, response bacterial infection. This contraction occurs absence other mucosal types. Instead, epithelium itself senses pathogen intrusion through a pattern recognition receptor complex—NAIP/NLRC4—and initiates actomyosin contractions...
Thiol-containing metabolites in all organisms are involved the regulation of diverse biological processes. We have developed a new method comprising bicyclobutane for chemoselective capturing and mass spectrometric analysis this compound class.
Salmonella Typhimurium (S.Tm) utilizes the chemotaxis receptor Tsr to exploit gut inflammation. However, characteristics of this exploitation and mechanism(s) employed by pathogen circumvent antimicrobial effects inflammation are poorly defined. Here, using different naturally occurring S.Tm strains (SL1344 14028) competitive infection experiments, we demonstrate that type-three secretion system (T3SS)-2 virulence is indispensable for beneficial Tsr-directed chemotaxis. The removal...
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Salmonella Typhimurium (S.Tm) is a common cause of self-limiting diarrhea. The mucosal inflammation thought to arise from standoff between the pathogen's virulence factors and host's innate immune defenses, particularly NAIP/NLRC4 inflammasome. However, it had remained unclear how this switches gut homeostasis inflammation. This was studied using streptomycin mouse model. S.Tm infections in knockout mice, cytokine inhibition –injection experiments revealed that caspase-1 (not -11) dependent...
Septins are filament-forming proteins important for organizing the cortex of animal and fungal cells. In mammals, 13 septin paralogues were recently shown to assemble into core heterohexamer heterooctamer complexes, which serve as building blocks apolar filamentous structures that differ among cell types. To determine how tissue-specific paralogue expression may shape heteromer repertoires thereby modulate properties filaments, we devised protocols analyze native heteromers with distinct...
Salmonella enterica serovar Typhimurium (S.Tm) infections of cultured cell lines have given rise to the ruffle model for epithelial invasion. According this model, Type-Three-Secretion-System-1 (TTSS-1) effectors SopB, SopE and SopE2 drive an explosive actin nucleation cascade, resulting in large lamellipodia- filopodia-containing ruffles cooperative S.Tm uptake. However, line experiments poorly recapitulate many tissue features encountered host's gut mucosa. Here, we employed bacterial...
Pathogenic gut bacteria are common causes of intestinal disease. Enteroids—cultured three-dimensional replicas the mammalian gut—offer an emerging model system to study disease mechanisms under conditions that recapitulate key features tract.
Recruitment of neutrophils into and across the gut mucosa is a cardinal feature intestinal inflammation in response to enteric infections. Previous work using model pathogen Salmonella enterica serovar Typhimurium ( S .Tm) established that invasion epithelial cells by .Tm leads recruitment lumen, where they can reduce loads transiently. Notably, fraction population survive this defense, re-grow high density, continue triggering enteropathy. However, functions intraluminal defense against...
Septin family proteins oligomerize through guanosine 5'-triphosphate-binding domains into core heteromers, which in turn polymerize at the cleavage furrow of dividing fungal and animal cells. assemblies during interphase cells remain poorly defined are topic this report. In study, we developed protocols for visualization authentic higher-order using tagged septins to effectively replace endogenous gene product within septin heteromers human Our analysis revealed that assemble...
Many Gram-negative bacteria use type III secretion systems to translocate effector proteins into host cells. These effectors interfere with cellular functions in a highly regulated manner resulting effects that are beneficial for the bacteria. The pathogen Yersinia can resist phagocytosis by eukaryotic cells translocating Yop target cell cytoplasm. This is called antiphagocytosis, and constitutes an important virulence feature of this since it allows survival immune rich lymphoid organs. We...