Entry of the bacterium Salmonella typhimurium into host cells requires membrane ruffling and rearrangement actin cytoskeleton. Here, it is shown that bacterial protein SipA plays a critical role in this process. binds directly to actin, decreases its concentration, inhibits depolymerization filaments. These activities result spatial localization more pronounced outward extension -induced ruffles, thereby facilitating uptake.

A central feature of Salmonella pathogenicity is the bacterium's ability to enter into non-phagocytic cells. Bacterial internalization consequence cellular responses characterized by Cdc42- and Rac-dependent actin cytoskeleton rearrangements. These are triggered co-ordinated function bacterial proteins delivered host cell a specialized protein secretion system termed type III. We report here that SopB, inositol polyphosphatase this system, mediates rearrangements entry in Cdc42-dependent...

Salmonella spp. have evolved the ability to enter into cells that are normally nonphagocytic. The internalization process is result of a remarkable interaction between bacteria and host cells. Immediately on contact, delivers number bacterial effector proteins cell cytosol through function specialized organelle termed type III secretion system. Initially, two delivered proteins, SopE SopB, stimulate small GTP-binding Cdc42 Rac. an exchange factor for these GTPases, SopB inositol...

The entry of Salmonella typhimurium into nonphagocytic cells requires a panel bacterial effector proteins that are delivered to the host cell via type III secretion system. These modulate host–cell signal-transduction pathways and actin cytoskeleton induce membrane ruffling internalization. One these effectors, termed SipA, is an actin-binding protein required for efficient cells. We report here SipA forms complex with T-plastin on infection. Formation such complex, which presence F-actin,...

Salmonella translocate a group of type III effectors into the host cells to induce entry, promote survival and cause intestinal inflammation. Although biochemical cellular mechanisms how bacterial function inside remain largely unknown, studies have indicated that likely strategy is exploit pathways through functional mimicry. We report here SopA, effector, mimics mammalian HECT E3 ubiquitin ligase. SopA preferentially uses UbcH5a, UbcH5c UbcH7 as E2s, which are involved in Both wild-type...

Skeletal myogenesis involves sequential activation, proliferation, self-renewal/differentiation and fusion of myogenic stem cells (satellite cells). Notch signaling is known to be essential for the maintenance satellite cells, but its function in late-stage myogenesis, i.e. post-differentiation myocytes post-fusion myotubes, unknown. Using stage-specific Cre alleles, we uncovered distinct roles Notch1 mononucleated multinucleated myotubes. Specifically, constitutive activation...

ABSTRACT Upon entry into the host, Salmonella enterica strains are presumed to encounter an iron-restricted environment. Consequently, these bacteria have evolved a variety of often-redundant high-affinity acquisition systems obtain iron in this restricted We identified transport system that is encoded within centisome 63 pathogenicity island typhimurium . The nucleotide composition locus significantly different from rest island, suggesting ancestry and mosaic structure for region S....

The enteric pathogen Salmonella enterica serovar Typhimurium causes food poisoning resulting in gastroenteritis. S. effector invasion protein A (SipA) promotes gastroenteritis by functional motifs that trigger either mechanisms of inflammation or bacterial entry. During infection intestinal epithelial cells, SipA was found to be responsible for the early activation caspase-3, an enzyme is required cleavage at a specific recognition motif divided into its two domains and activated manner...

Confocal and immunoelectron microscopic analysis of urethral exudates from 12 men with gonococcal urethritis showed that Neisseria gonorrhoeae can invade epithelial cells. Studies acridine orange stain demonstrated the majority organisms within cells were viable at time fixation. Three-dimensional modeling an infected cell using image 21 digitized confocal sections stained YOYO-1 DiIC18(3) revealed invasion these occurred in a polar fashion, most likely luminal surface. Serial micrographs...

Many microbial pathogens deliver effector proteins via the type III secretion system into infected host cells. Elucidating function of these effectors is essential for our understanding pathogenesis. Here, we describe biochemical and structural characterization an protein (NleL) from Escherichia coli O157:H7, a widespread pathogen causing severe foodborne diseases. We show that NleL functionally structurally mimics eukaryotic HECT E3 ligases catalyzes formation unanchored polyubiquitin...

Salmonella enterica serovar Typhimurium invade non-phagocytic cells by injecting bacterial effector proteins to exploit the host actin cytoskeleton network. SipC is such a known nucleate actin, bundle F-actin, and translocate type III effectors. The molecular mechanism of how bundles F-actin domains responsible for these activities are not well characterized. We successfully separated through series genetic deletion/insertions in SipC. found that C terminus (amino acids 200–409) bundled...

This study aimed to explore the causal association between imaging measurement indicators of major internal organs and liver lesions using a two-sample Mendelian randomization (MR) method. Data from UK Biobank GWAS Catalog platform were used select single nucleotide polymorphisms (SNPs) associated with MRI or derived results various organ as genetic instrumental variables. FinnGen project's R9 version lesion outcomes, such nonalcoholic fatty disease (NAFLD), cirrhosis, primary hepatocellular...

The current model for pathogenesis of inhalation anthrax indicates that the uptake and fate Bacillus anthracis spores in alveolar macrophages are critical to infection process. We have employed primary macrophages, which more efficient spore than macrophage-like cell line RAW264.7, investigate survival. found at a multiplicity (moi) 5, greater 80% Sterne strain containing only pXO1 plasmid were internalized within 1 h. Within 4 h post infection, viability decreased approximately 40%....

Serum-sensitive Neisseria gonorrhoeae strains become serum resistant when grown in the presence of a sialic acid precursor, cytidine monophospho-N-acetylneuraminic acid. We examined abilities human neutrophils to phagocytose sialylated and nonsialylated gonococci observed decrease complement-dependent phagocytosis compared with that (50.7 versus 25.9% survival at 30 min). This opsonophagocytosis after sialylation may contribute pathogenicity gonococcal infections.

Salmonella are able to invade non-phagocytic cells such as intestinal epithelial by modulating the host actin cytoskeleton produce membrane ruffles. Two type III effector proteins SopB and SopE play key roles this modulation. is a known guanine nucleotide exchange factor (GEF) capable of activating Rac1 CDC42. phosphatidylinositol 4-phosphatase 5-phosphatase promoting ruffles invasion through undefined mechanisms. Previous studies have demonstrated that activity required for...

Salmonella entry into epithelial host cells results from the actin cytoskeleton reorganization that is induced by a group of bacterial proteins delivered to type III secretion system. SopE, SopE2 and SopB activate CDC42 Rac1 intercept signal transduction pathways involved in rearrangements. SipA SipC directly bind modulate dynamics facilitating entry. Biochemical studies have indicated decreases critical concentration for polymerization may be promoting initial Salmonella-induced...

Summary Salmonella type III secreted SipC possesses dual functions: translocation of effectors and actin modulation. The biological significance SipC's nucleation activity in ‐induced cytoskeleton rearrangements has not been studied. We report here the delineation from effector SipC. Our data show that central amino acid region (residues: 201–220) is essential for its C‐terminal (321–409) required effectors. A nucleation‐deficient mutant, which maintained activity, was obtained. This mutant...

Salmonella translocate bacterial effectors into host cells to confer entry and survival. It is not known how the cope with influx of these effectors. We report here that effector, SopA, interacts HsRMA1, a ubiquitin E3 ligase previously unknown function. SopA ubiquitinated degraded by HsRMA1-mediated ubiquitination pathway. A sopA mutant escapes out Salmonella-containing vacuoles less frequently cytosol than wild type in HeLa HsRMA1-dependent manner. Our data suggest efficient escape...

Salmonella enterica serovar Typhimurium invades non‐phagocytic cells by inducing macropinocytosis. SopB is involved in modulating actin dynamics to promote ‐induced invasion. We report here that SopB‐generated PtdIns(3) P binds VAMP8/endobrevin efficient bacterial phagocytosis. VAMP8 recruited macropinosomes a nocodazole‐dependent, but Brefeldin A‐independent, manner. found directly and colocalizes with . The inositol phosphatase activity of required for accumulation, while wortmannin,...

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and may result in potentially fatal hemolytic uremia syndrome humans. EHEC colonize the intestinal mucosa promote formation of actin-rich pedestals via translocated type III effectors. Two secreted effectors, Tir EspFu/TccP, are key players for pedestal formation. We discovered that an effector protein called Non-LEE-encoded Ligase (NleL) is E3 ubiquitin ligase. In vitro, we showed NleL C753 residue critical its...

The delivery of effector proteins by Salmonella across the host cell membrane requires a subset effectors secreted type III secretion system (TTSS) known as translocators. SipC and SipB are translocator that inserted into membranes presumably form channel translocates cell. molecular events how these translocators insert remain unknown. We have previously shown C-terminal amino acid region (321-409) is required for translocation cells. In this study, we demonstrate ability to SipC-SipB...