Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular pathogen that damages gastrointestinal tissue and causes severe diarrhoea. The mechanisms by which Salmonella disrupts epithelial barrier and increases the paracellular permeability are incompletely understood. Our present study aims to determine the role of Gli1, a transcription factor activated in the sonic hedgehog (Shh) pathway, in decreasing the levels of apical junction proteins in a Salmonella-infected human colonic epithelial cancer cell line, Caco-2, and in the intestinal tissue of Salmonella-infected mice. Here, we report that S. Typhimurium increased the mRNA and protein levels of Gli1 and Snail, a downstream transcription factor that plays an important role in the epithelial-to-mesenchymal transition (EMT). S. Typhimurium also decreased the levels of E-cadherin and three tight junction proteins (ZO-1, claudin-1, and occludin). Gli1 siRNA and GANT61, a Gli1-specific inhibitor, blocked S. Typhimurium-induced Snail expression, restored the levels of E-cadherin and tight junction proteins, and prevented S. Typhimurium-increased paracellular permeability. Further study showed that Gli1 was cross-activated by the MAP and PI-3 kinase pathways. S. Typhimurium devoid of sopB, an effector of the Type 3 secretion system (T3SS) responsible for AKT activation, was unable to induce Snail expression and to decrease the expression of apical junction proteins. Our study uncovered a novel role of Gli1 in mediating the Salmonella-induced disruption of the intestinal epithelial barrier.

Hepatitis B virus persistence is related to the immense production of subviral particles (SVPs) build up by its S (HBV.S) envelope protein. Here we demonstrate that HBV.S utilizes the host COPII complex for ER export. Among the different COPII isoform components, HBV.S selectively hijacks Sec24A and Sec23B along with Sar1/Sec13/Sec31 to travel to SVP assembly sites at the ERGIC. Functional dissection of the pathogen—host crosstalk revealed a novel ER export code, a di-arginine motif of HBV.S, recognized by Sec24A.

Infections with protozoan and helminthic parasites affect multiple organs in the mammalian host. Imaging pathogens in their natural environment takes a more holistic view on biomedical aspects of parasitic infections. Here, we focus on selected organs of the thoracic and abdominopelvic cavities most commonly affected by parasites. Parasitic infections of these organs are often associated with severe medical complications or have health implications beyond the infected individual. Intravital imaging has provided a more dynamic picture of the host-parasite interplay and contributed not only to our understanding of the various disease pathologies, but has also provided fundamental insight into the biology of the parasites.

Investigation of cytoskeleton during bacterial infection has significantly contributed to both cell and infection biology. Bacterial pathogens Listeria monocytogenes and Shigella flexneri are widely recognised as paradigms for investigation of the cytoskeleton during bacterial entry, actin-based motility, and cell-autonomous immunity. At the turn of the century, septins were a poorly understood component of the cytoskeleton mostly studied in the context of yeast cell division and human cancer. In 2002, a screen performed in the laboratory of Pascale Cossart identified septin family member MSF (MLL septin-like fusion, now called SEPT9) associated with L. monocytogenes entry into human epithelial cells. These findings inspired the investigation of septins during L. monocytogenes and S. flexneri infection at the Institut Pasteur, illuminating important roles for septins in host-microbe interactions. In this review, we revisit the history of septin biology and bacterial infection, and discuss how the comparative study of L. monocytogenes and S. flexneri has been instrumental to understand septin roles in cellular homeostasis and host defence.

Extracellular bacterial symbionts communicate biochemically with their hosts to establish niches that foster the partnership. Using quantitative ion microprobe isotopic imaging (nanoscale secondary ion mass spectrometry [NanoSIMS]), we surveyed localization of 15 N-labelled molecules produced by the bacterium Vibrio fischeri within the cells of the symbiotic organ of its host, the Hawaiian bobtail squid, and compared that with either labelled non-specific species or amino acids. In all cases, two areas of the organ's epithelia were significantly more 15 N enriched: (a) surface ciliated cells, where environmental symbionts are recruited, and (b) the organ's crypts, where the symbiont population resides in the host. Label enrichment in all cases was strongest inside host cell nuclei, preferentially in the euchromatin regions and the nucleoli. This permissiveness demonstrated that uptake of biomolecules is a general mechanism of the epithelia, but the specific responses to V. fischeri cells recruited to the organ's surface are due to some property exclusive to this species. Similarly, in the organ's deeper crypts, the host responds to common bacterial products that only the specific symbiont can present in that location. The application of NanoSIMS allows the discovery of such distinct modes of downstream signalling dependent on location within the host and provides a unique opportunity to study the microbiogeographical patterns of symbiotic dialogue.

A fundamental question of eukaryotic cell biology is how membrane organelles are organised and interact with each other. Cell biologists address these questions by characterising the structural features of membrane compartments and the mechanisms that coordinate their exchange. To do so, they must rely on variety of cargo molecules and treatments that enable targeted perturbation, localisation, and labelling of specific compartments. In this context, bacterial toxins emerged in cell biology as paradigm shifting molecules that enabled scientists to not only study them from the side of bacterial infection but also from the side of the mammalian host. Their selectivity, potency, and versatility made them exquisite tools for uncovering much of our current understanding of membrane trafficking mechanisms. Here, we will follow the steps that lead toxins until their intracellular targets, highlighting how specific events helped us comprehend membrane trafficking and establish the fundamentals of various cellular organelles and processes. Bacterial toxins will continue to guide us in answering crucial questions in cellular biology while also acting as probes for new technologies and applications.

The Gram-negative bacterium Xanthomonas campestris pv. vesicatoria translocates effector proteins via a type III secretion system (T3SS) into eukaryotic cells. The T3SS spans both bacterial membranes and consists of more than 20 proteins, 9 of which are conserved in plant and animal pathogens and constitute the core subunits of the secretion apparatus. T3S in X. campestris pv. vesicatoria also depends on nonconserved proteins with yet unknown function including HrpB7, which contains predicted N- and C-terminal coiled-coil regions. In the present study, we provide experimental evidence that HrpB7 forms stable oligomeric complexes. Interaction and localisation studies suggest that HrpB7 interacts with inner membrane and predicted cytoplasmic (C) ring components of the T3SS but is dispensable for the assembly of the C ring. Additional interaction partners of HrpB7 include the cytoplasmic adenosinetriphosphatase HrcN and the T3S chaperone HpaB. The interaction of HrpB7 with T3SS components as well as complex formation by HrpB7 depends on the presence of leucine heptad motifs, which are part of the predicted N- and C-terminal coiled-coil structures. Our data suggest that HrpB7 forms multimeric complexes that associate with the T3SS and might serve as a docking site for the general T3S chaperone HpaB.