Tracking Pathogen Infections by Time-Resolved Chemical Proteomics.

Studying the dynamic interaction between host cells and pathogen is vital but remains technically challenging. We describe herein a time-resolved chemical proteomics strategy enabling host and pathogen temporal interaction profiling (HAPTIP) for tracking the entry of a pathogen into the host cell. A novel multifunctional chemical proteomics probe was introduced to label living bacteria followed by in vivo crosslinking of bacteria proteins to their interacting host-cell proteins at different time points initiated by UV for label-free quantitative proteomics analysis.

YshB Promotes Intracellular Replication and Is Required for Virulence.

virulence requires the initial invasion of host cells, followed by modulation of the intracellular environment for survival and replication. In an effort to characterize the role of small RNAs in pathogenesis, we inadvertently identified a 5-kDa protein named YshB that is involved in the intracellular survival of We show here that expression is upregulated upon entry into macrophages. When expression is upregulated before bacterial entry, invasion efficiency is inhibited.

Corrigendum: Organoid and Enteroid Modeling of Infection.

[This corrects the article DOI: 10.3389/fcimb.2018.

Methylthioadenosine Suppresses Salmonella Virulence.

In order to deploy virulence factors at appropriate times and locations, microbes must rapidly sense and respond to various metabolite signals. Previously, we showed a transient elevation of the methionine-derived metabolite methylthioadenosine (MTA) concentration in serum during systemic serovar Typhimurium infection. Here we explored the functional consequences of increased MTA concentrations on Typhimurium virulence.

Organoid and Enteroid Modeling of Infection.

are Gram-negative rod-shaped facultative anaerobic bacteria that are comprised of over 2,000 serovars. They cause gastroenteritis (salmonellosis) with headache, abdominal pain and diarrhea clinical symptoms. Salmonellosis brings a heavy burden for the public health in both developing and developed countries.

Identification of a Novel Type III Effector by Quantitative Secretome Profiling.

serovar Typhimurium is arguably one of the most studied bacterial pathogens and successful infection requires the delivery of its virulence factors (effectors) directly into host cells via the type III secretion systems (T3SSs). Central to pathogenesis, these effector proteins have been subjected to extensive studies over the years. Nevertheless, whether additional effectors exist remains unclear.

InvS Coordinates Expression of PrgH and FimZ and Is Required for Invasion of Epithelial Cells by Salmonella enterica serovar Typhimurium.

Deep sequencing has revolutionized our understanding of the bacterial RNA world and has facilitated the identification of 280 small RNAs (sRNAs) in Despite the suspicions that sRNAs may play important roles in pathogenesis, the functions of most sRNAs remain unknown. To advance our understanding of RNA biology in virulence, we searched for sRNAs required for bacterial invasion into nonphagocytic cells. After screening 75 sRNAs, we discovered that the ablation of InvS caused a significant decrease of invasion into epithelial cells.

Stage-specific effects of Notch activation during skeletal myogenesis.

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 of satellite cells, but its function in late-stage myogenesis, i.e.

Dual 4- and 5-phosphatase activities regulate SopB-dependent phosphoinositide dynamics to promote bacterial entry.

Salmonella are able to invade non-phagocytic cells such as intestinal epithelial cells by modulating the host actin cytoskeleton to produce membrane ruffles. Two type III effector proteins SopB and SopE play key roles to this modulation. SopE is a known guanine nucleotide exchange factor (GEF) capable of activating Rac1 and CDC42.

Genomic comparison of Salmonella typhimurium DT104 with non-DT104 strains.

DT104 emerged as a new branch of Salmonella typhimurium with resistance to multiple antimicrobials. To reveal some general genomic features of DT104 for clues of evolutionary events possibly associated with the emergence of this relatively new type of this pathogen, we mapped 11 independent DT104 strains and compared them with non-DT104 S. typhimurium strains.

Erratum: Salmonella type III effector SopB modulates host cell exocytosis.

[This corrects the article DOI: 10.1038/emi.2013.

Salmonella type III effector SopB modulates host cell exocytosis.

Salmonella enterica pathogenesis is dependent on its ability to enter and replicate inside host cells. Replication occurs inside the Salmonella-containing vacuole (SCV), a vacuolar compartment that is modified by bacterial effectors secreted through the two type III secretion systems (T3SS-1 and T3SS-2). Type III effectors interact with the host cell endocytic pathway to aid replication.

SipB-SipC complex is essential for translocon formation.

The delivery of effector proteins by Salmonella across the host cell membrane requires a subset of effectors secreted by the type III secretion system (TTSS) known as translocators. SipC and SipB are translocator proteins that are inserted into host membranes and presumably form a channel that translocates type III effectors into the host cell. The molecular events of how these translocators insert into the host cell membrane remain unknown.

The actin-polymerizing activity of SipA is not essential for Salmonella enterica serovar Typhimurium-induced mucosal inflammation.

Salmonella enterica serovar Typhimurium depends on type III secretion systems to inject effector proteins into host cells to promote bacterial invasion and to induce intestinal inflammation. SipA, a type III effector, is known to play important roles in both the invasion and the elicitation of intestinal inflammation. The actin-modulating activity of SipA has been shown to promote Salmonella entry into epithelial cells.

Interactions of bacterial proteins with host eukaryotic ubiquitin pathways.

Ubiquitination is a post-translational modification in which one or more 76 amino acid polypeptide ubiquitin molecules are covalently linked to the lysine residues of target proteins. Ubiquitination is the main pathway for protein degradation that governs a variety of eukaryotic cellular processes, including the cell-cycle, vesicle trafficking, antigen presentation, and signal transduction. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of many diseases including inflammatory and neurodegenerative disorders.

The EHEC type III effector NleL is an E3 ubiquitin ligase that modulates pedestal formation.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and may result in potentially fatal hemolytic uremia syndrome in humans. EHEC colonize the intestinal mucosa and promote the formation of actin-rich pedestals via translocated type III effectors. Two EHEC type III secreted effectors, Tir and EspFu/TccP, are key players for pedestal formation.

Salmonella pathogenesis and processing of secreted effectors by caspase-3.

The enteric pathogen Salmonella enterica serovar Typhimurium causes food poisoning resulting in gastroenteritis. The S. Typhimurium effector Salmonella invasion protein A (SipA) promotes gastroenteritis by functional motifs that trigger either mechanisms of inflammation or bacterial entry.

Involvement of TIP60 acetyltransferase in intracellular Salmonella replication.

Background: Salmonella enterica is a facultative intracellular pathogen that replicates within a membrane-bound compartment termed Salmonella containing vacuole (SCV). The biogenesis of SCV requires Salmonella type III protein secretion/translocation system and their effector proteins which are translocated into host cells to exploit the vesicle trafficking pathways. SseF is one of these effectors required for SCV formation and Intracellular Salmonella replication through unknown mechanisms.

The C terminus of SipC binds and bundles F-actin to promote Salmonella invasion.

Salmonella enterica serovar Typhimurium invade non-phagocytic cells by injecting bacterial effector proteins to exploit the host actin cytoskeleton network. SipC is such a Salmonella effector known to nucleate actin, bundle F-actin, and translocate type III effectors. The molecular mechanism of how SipC bundles F-actin and SipC domains responsible for these activities are not well characterized.

Crystal structure of SopA, a Salmonella effector protein mimicking a eukaryotic ubiquitin ligase.

Bacterial pathogens deliver virulence proteins into host cells to facilitate entry and survival. Salmonella SopA functions as an E3 ligase to manipulate the host proinflammatory response. Here we report the crystal structure of SopA in two conformations.

SipC multimerization promotes actin nucleation and contributes to Salmonella-induced inflammation.

Actin nucleation is the rate-limiting step in actin assembly and is regulated by actin-binding proteins and signal transduction molecules. Salmonella enterica serovar Typhimurium exploits actin dynamics by reorganizing the host actin cytoskeleton to facilitate its own uptake. SipC is a Salmonella actin-binding protein that nucleates actin filament formation in vitro.

Bacteria-generated PtdIns(3)P recruits VAMP8 to facilitate phagocytosis.

Salmonella enterica serovar Typhimurium invades non-phagocytic cells by inducing macropinocytosis. SopB is involved in modulating actin dynamics to promote Salmonella-induced invasion. We report here that SopB-generated PtdIns(3)P binds VAMP8/endobrevin to promote efficient bacterial phagocytosis.

Exo70 interacts with the Arp2/3 complex and regulates cell migration.

The exocyst is a multiprotein complex essential for tethering secretory vesicles to specific domains of the plasma membrane for exocytosis. Here, we report that the exocyst component Exo70 interacts with the Arp2/3 complex, a key regulator of actin polymerization. We further show that the exocyst-Arp2/3 interaction is regulated by epidermal growth factor (EGF) signalling.