scholarly journals A LiveSalmonellaVaccine Delivering PcrV through the Type III Secretion System Protects againstPseudomonas aeruginosa

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Julia Aguilera-Herce ◽  
Meritxell García-Quintanilla ◽  
Rocío Romero-Flores ◽  
Michael J. McConnell ◽  
Francisco Ramos-Morales
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Opportunistic Pathogen ◽  
Host Cells ◽  
Gram Negative ◽  
Content Type ◽  
Specific Antibodies ◽  
Type Iii ◽  
Serovar Typhimurium

ABSTRACTPseudomonas aeruginosais a common Gram-negative opportunistic pathogen that is intrinsically resistant to a wide range of antibiotics. The development of a broadly protective vaccine againstP. aeruginosaremains a major challenge. Here, we used an attenuated strain ofSalmonella entericaserovar Typhimurium as a vehicle to expressP. aeruginosaantigens. A fusion between theS. entericatype III secretion effector protein SseJ and theP. aeruginosaantigen PcrV expressed under the control of thesseApromoter was translocated bySalmonellainto host cellsin vitroand elicited the generation of specific antibodies in mice. Mice immunized with attenuatedSalmonellaexpressing this fusion had reduced bacterial loads in the spleens and lungs and lower serum levels of proinflammatory cytokines than control mice afterP. aeruginosainfection. Importantly, immunized mice also showed significantly enhanced survival in this model. These results suggest that type III secretion effectors ofS. entericaare appropriate carriers in the design of a live vaccine to prevent infections caused byP. aeruginosa.IMPORTANCEThe Gram-negative bacteriumPseudomonas aeruginosais an important opportunistic pathogen that causes infections in cystic fibrosis and hospitalized patients. Therapeutic treatments are limited due to the emergence and spread of new antibiotic-resistant strains. In this context, the development of a vaccine is a priority. Here, we used an attenuated strain ofSalmonella entericaserovar Typhimurium as a vehicle to express and deliver thePseudomonasantigen PcrV. This vaccine induced the generation of specific antibodies in mice and protected them from lethal infections withP. aeruginosa. This is an important step toward the development of an effective vaccine for the prevention of infections caused byP. aeruginosain humans.

scholarly journals Cytosporone B, an Inhibitor of the Type III Secretion System of Salmonella enterica Serovar Typhimurium

2013 ◽  
Vol 57 (5) ◽  
pp. 2191-2198 ◽  
Author(s):  
Jianfang Li ◽  
Chao Lv ◽  
Weiyang Sun ◽  
Zhenyu Li ◽  
Xiaowei Han ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Bacterial Resistance ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Effector Proteins ◽  
Host Cells ◽  
Content Type ◽  
Type Iii ◽  
Serovar Typhimurium

ABSTRACTBacterial virulence factors have been increasingly regarded as attractive targets for development of novel antibacterial agents. Virulence inhibitors are less likely to generate bacterial resistance, which makes them superior to traditional antibiotics that target bacterial viability.Salmonella entericaserovar Typhimurium, an important food-borne human pathogen, has type III secretion system (T3SS) as its major virulence factor. T3SS secretes effector proteins to facilitate invasion into host cells. In this study, we identified several analogs of cytosporone B (Csn-B) that strongly block the secretion ofSalmonellapathogenicity island 1 (SPI-1)-associated effector proteins, without affecting the secretion of flagellar protein FliCin vitro. Csn-B and two other derivatives exhibited a strong inhibitory effect on SPI-1-mediated invasion to HeLa cells, while no significant toxicity to bacteria was observed. Nucleoid proteins Hha and H-NS bind to the promoters of SPI-1 regulator geneshilD,hilC, andrtsAto repress their expression and consequently regulate the expression of SPI-1 apparatus and effector genes. We found that Csn-B upregulated the transcription ofhhaandhns, implying that Csn-B probably affected the secretion of effectors through the Hha–H-NS regulatory pathway. In summary, this study presented an effective SPI-1 inhibitor, Csn-B, which may have potential in drug development against antibiotic-resistantSalmonella.

scholarly journals Secretion of Flagellar Proteins by the Pseudomonas aeruginosa Type III Secretion-Injectisome System

2015 ◽  
Vol 197 (12) ◽  
pp. 2003-2011 ◽  
Author(s):  
Dilek Ince ◽  
Fayyaz S. Sutterwala ◽  
Timothy L. Yahr
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Bacterial Species ◽  
Opportunistic Pathogen ◽  
Host Cells ◽  
Inflammasome Activation ◽  
Content Type ◽  
Type Iii ◽  
Amino Terminal ◽  
Flagellar Proteins

ABSTRACTThe opportunistic pathogenPseudomonas aeruginosautilizes an injectisome-type III secretion system (injectisome-T3SS) to elicit cytotoxicity toward epithelial cells and macrophages. Macrophage killing results from the cytotoxic properties of the translocated effector proteins (ExoS, ExoT, ExoU, and ExoY) and inflammasome-mediated induction of pyroptosis. Inflammasome activation can occur following Nlrc4-mediated recognition of cytosolic translocated flagellin (FliC). In the present study, we demonstrate that FliC is a secretion substrate of both the injectisome- and flagellum-associated T3SSs. Molecular analyses indicate that the first 20 amino-terminal residues of FliC are sufficient for secretion by the injectisome-T3SS and that the first 100 residues are sufficient for translocation of FliC into host cells. Although maximal inflammasome activation requires FliC, activation can also occur in the absence of FliC. This prompted us to examine whether other flagellar components might also be translocated into cells to elicit inflammasome activation. Indeed, we find that the flagellar cap (FliD), hook-associated (FlgK and FlgL), hook (FlgE), and rod (FlgE) proteins are secretion substrates of the injectisome-T3SS. None of these proteins, however, result in increased inflammasome activation when they are overexpressed in afliCmutant and appear to be translocated into host cells. While a role in inflammasome activation has been excluded, these data raise the possibility that flagellar components, which are highly conserved between different bacterial species, trigger other specific host responses from the extracellular milieu or contribute to the pathogenesis ofP. aeruginosa.IMPORTANCEThe inflammasome is a host defense mechanism that recognizes invading bacteria and triggers an inflammatory immune response. The opportunistic pathogenP. aeruginosaproduces both inflammasome agonists and antagonists. In this study, we demonstrate that overexpression of an agonist suppresses the activity of an antagonist, thereby resulting in inflammasome activation. Since the relative expression levels of agonists and antagonists likely vary between strains, these differences could be important predictors of whether a particularP. aeruginosastrain elicits inflammasome activation.

scholarly journals Identification of Salmonella Pathogenicity Island-2 Type III Secretion System Effectors Involved in Intramacrophage Replication of S. enterica Serovar Typhimurium: Implications for Rational Vaccine Design

mBio ◽  
2013 ◽  
Vol 4 (2) ◽  
Author(s):  
Rita Figueira ◽  
Kathryn G. Watson ◽  
David W. Holden ◽  
Sophie Helaine
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Host Cells ◽  
Content Type ◽  
Type Iii ◽  
Serovar Typhimurium ◽  
Bacterial Replication ◽  
Heterologous Antigens

ABSTRACT Salmonella enterica serovars cause severe diseases in humans, such as gastroenteritis and typhoid fever. The development of systemic disease is dependent on a type III secretion system (T3SS) encoded by Salmonella pathogenicity island-2 (SPI-2). Translocation of effector proteins across the Salmonella-containing vacuole, via the SPI-2 T3SS, enables bacterial replication within host cells, including macrophages. Here, we investigated the contribution of these effectors to intramacrophage replication of Salmonella enterica serovar Typhimurium using Fluorescence Dilution, a dual-fluorescence tool which allows direct measurement of bacterial replication. Of 32 strains, each carrying single mutations in genes encoding effectors, 10 (lacking sifA, sseJ, sopD2, sseG, sseF, srfH, sseL, spvD, cigR, or steD) were attenuated in replication in mouse bone marrow-derived macrophages. The replication profiles of strains combining deletions in effector genes were also investigated: a strain lacking the genes sseG, sopD2, and srfH showed an increased replication defect compared to single-mutation strains and was very similar to SPI-2 T3SS-deficient bacteria with respect to its replication defect. This strain was substantially attenuated in virulence in vivo and yet retained intracellular vacuole integrity and a functional SPI-2 T3SS. Moreover, this strain was capable of SPI-2 T3SS-mediated delivery of a model antigen for major histocompatibility complex (MHC) class I-dependent T-cell activation. This work establishes a basis for the use of a poly-effector mutant strain as an attenuated vaccine carrier for delivery of heterologous antigens directly into the cytoplasm of host cells. IMPORTANCE Live attenuated strains of Salmonella enterica serotype Typhi have generated much interest in the search for improved vaccines against typhoid fever and as vaccine vectors for the delivery of heterologous antigens. A promising vaccine candidate is the ΔaroC ΔssaV S. Typhi strain, which owes its attenuation mainly to lack of a type III secretion system (SPI-2 T3SS). The SPI-2 T3SS is important for bacterial proliferation inside macrophages, but not all of the effectors involved in this process have been identified. Here, we show that 10 effectors of the related strain S. Typhimurium contribute to intracellular replication in macrophages. Moreover, we establish that a poly-effector mutant strain of S. Typhimurium can have a severe replication defect and maintain a functional SPI-2 T3SS, which can be exploited for delivery of heterologous antigens.

scholarly journals RNase E Promotes Expression of Type III Secretion System Genes in Pseudomonas aeruginosa

2019 ◽  
Vol 201 (22) ◽  
Author(s):  
Josh S. Sharp ◽  
Arne Rietsch ◽  
Simon L. Dove
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Effector Proteins ◽  
Host Cells ◽  
Rnase E ◽  
Content Type ◽  
Type Iii ◽  
Small Regulatory Rnas

ABSTRACT Pseudomonas aeruginosa is an important opportunistic pathogen that employs a type III secretion system (T3SS) to inject effector proteins into host cells. Using a protein depletion system, we show that the endoribonuclease RNase E positively regulates expression of the T3SS genes. We also present evidence that RNase E antagonizes the expression of genes of the type VI secretion system and limits biofilm production in P. aeruginosa. Thus, RNase E, which is thought to be the principal endoribonuclease involved in the initiation of RNA degradation in P. aeruginosa, plays a key role in controlling the production of factors involved in both acute and chronic stages of infection. Although the posttranscriptional regulator RsmA is also known to positively regulate expression of the T3SS genes, we find that RNase E does not appreciably influence the abundance of RsmA in P. aeruginosa. Moreover, we show that RNase E still exerts its effects on T3SS gene expression in cells lacking all four of the key small regulatory RNAs that function by sequestering RsmA. IMPORTANCE The type III secretion system (T3SS) is a protein complex produced by many Gram-negative pathogens. It is capable of injecting effector proteins into host cells that can manipulate cell metabolism and have toxic effects. Understanding how the T3SS is regulated is important in understanding the pathogenesis of bacteria with such systems. Here, we show that RNase E, which is typically thought of as a global regulator of RNA stability, plays a role in regulating the T3SS in Pseudomonas aeruginosa. Depleting RNase E results in the loss of T3SS gene expression as well as a concomitant increase in biofilm formation. These observations are reminiscent of the phenotypes associated with the loss of activity of the posttranscriptional regulator RsmA. However, RNase E-mediated regulation of these systems does not involve changes in the abundance of RsmA and is independent of the known small regulatory RNAs that modulate RsmA activity.

scholarly journals Edwardsiella tarda-Induced Cytotoxicity Depends on Its Type III Secretion System and Flagellin

2014 ◽  
Vol 82 (8) ◽  
pp. 3436-3445 ◽  
Author(s):  
Hai-Xia Xie ◽  
Jin-Fang Lu ◽  
Nathalie Rolhion ◽  
David W. Holden ◽  
Pin Nie ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Host Cells ◽  
Edwardsiella Tarda ◽  
Dependent Manner ◽  
Gram Negative ◽  
Content Type ◽  
Murine Bone Marrow ◽  
Type Iii

ABSTRACTMany Gram-negative bacteria utilize a type III secretion system (T3SS) to translocate virulence proteins into host cells to cause diseases. In responding to infection, macrophages detect some of the translocated proteins to activate caspase-1-mediated cell death, called pyroptosis, and secretion of proinflammatory cytokines to control the infection.Edwardsiella tardais a Gram-negative enteric pathogen that causes hemorrhagic septicemia in fish and both gastrointestinal and extraintestinal infections in humans. In this study, we report that the T3SS ofE. tardafacilitates its survival and replication in murine bone marrow-derived macrophages, andE. tardainfection triggers pyroptosis of infected macrophages from mice and fish and increased secretion of the cytokine interleukin 1β in a T3SS-dependent manner. Deletion of the flagellin genefliCofE. tardaresults in decreased cytotoxicity for infected macrophages and does not attenuate its virulence in a fish model of infection, whereas upregulated expression of FliC in thefliCmutant strain reduces its virulence. We propose that the host controlsE. tardainfection partially by detecting FliC translocated by the T3SS, whereas the bacteria downregulate the expression of FliC to evade innate immunity.

scholarly journals The Actin-Polymerizing Activity of SipA Is Not Essential for Salmonella enterica Serovar Typhimurium-Induced Mucosal Inflammation

2013 ◽  
Vol 81 (5) ◽  
pp. 1541-1549 ◽  
Author(s):  
Dongju Li ◽  
Xueqin Wang ◽  
Lu Wang ◽  
Daoguo Zhou
Keyword(s):  
Inflammatory Response ◽  
Mouse Model ◽  
Salmonella Enterica ◽  
Intestinal Inflammation ◽  
Host Cells ◽  
Bacterial Invasion ◽  
Content Type ◽  
Type Iii ◽  
Serovar Typhimurium ◽  
Mouse Model Of Infection

ABSTRACTSalmonella entericaserovar 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 promoteSalmonellaentry into epithelial cells. To investigate whether the actin-modulating activity of SipA is required for its ability to induce an inflammatory responsein vivo, we generated the SipAK635A E637Wmutant, which is deficient in actin-modulating activity.Salmonellastrains expressing the chromosomal SipAK635A E637Wpoint mutation had reduced invasion abilities but still caused colitis similar to that caused by the wild-type strain in a mouse model of infection. Our data indicate that the SipA actin-polymerizing activity is not essential for the SipA-induced inflammatory response in the mouse model of infection.

scholarly journals Mutations in the Pseudomonas aeruginosa Needle Protein GenepscFConfer Resistance to Phenoxyacetamide Inhibitors of the Type III Secretion System

2014 ◽  
Vol 58 (4) ◽  
pp. 2211-2220 ◽  
Author(s):  
Nicholas O. Bowlin ◽  
John D. Williams ◽  
Claire A. Knoten ◽  
Matthew C. Torhan ◽  
Tommy F. Tashjian ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Molecular Target ◽  
Secretion System ◽  
Host Cells ◽  
Content Type ◽  
Type Iii ◽  
Unknown Protein ◽  
Needle Protein

ABSTRACTThe type III secretion system (T3SS) is a clinically important virulence mechanism inPseudomonas aeruginosathat secretes and translocates effector toxins into host cells, impeding the host's rapid innate immune response to infection. Inhibitors of T3SS may be useful as prophylactic or adjunctive therapeutic agents to augment the activity of antibiotics inP. aeruginosainfections, such as pneumonia and bacteremia. One such inhibitor, the phenoxyacetamide MBX 1641, exhibits very responsive structure-activity relationships, including striking stereoselectivity, in its inhibition ofP. aeruginosaT3SS. These features suggest interaction with a specific, but unknown, protein target. Here, we identify the apparent molecular target by isolating inhibitor-resistant mutants and mapping the mutation sites by deep sequencing. Selection and sequencing of four independent mutants resistant to the phenoxyacetamide inhibitor MBX 2359 identified the T3SS genepscF, encoding the needle apparatus, as the only locus of mutations common to all four strains. Transfer of the wild-type and mutated alleles ofpscF, together with its chaperone and cochaperone genespscEandpscG, to a ΔpscF P. aeruginosastrain demonstrated that each of the single-codon mutations inpscFis necessary and sufficient to provide secretion and translocation that is resistant to a variety of phenoxyacetamide inhibitor analogs but not to T3SS inhibitors with different chemical scaffolds. These results implicate the PscF needle protein as an apparent new molecular target for T3SS inhibitor discovery and suggest that three other chemically distinct T3SS inhibitors interact with one or more different targets or a different region of PscF.

scholarly journals Killing of Candida albicans Filaments by Salmonella enterica Serovar Typhimurium Is Mediated by sopB Effectors, Parts of a Type III Secretion System

2011 ◽  
Vol 10 (6) ◽  
pp. 782-790 ◽  
Author(s):  
Younghoon Kim ◽  
Eleftherios Mylonakis
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Critical Role ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Content Type ◽  
Type Iii ◽  
Serovar Typhimurium ◽  
Fungal Interactions

ABSTRACTAlthough bacterial-fungal interactions shape microbial virulence during polymicrobial infections, only a limited number of studies have evaluated this interaction on a genetic level. We report here that one interaction is mediated bysopB, an effector of a type III secretion system (TTSS) ofSalmonella entericaserovar Typhimurium. In these studies, we screened 10 TTSS effector-related mutants and determined their role in the killing ofC. albicansfilamentsin vitroduring coinfection in planktonic environments. We found that deleting thesopBgene (which encodes inositol phosphatase) was associated with a significant decrease inC. albicanskilling at 25°C after 5 days, similar to that caused by the deletion ofsipB(which encodes TTSS translocation machinery components). ThesopBdeletion dramatically influenced the killing ofC. albicansfilaments. It was associated with repressed filamentation in theCaenorhabditis elegansmodel ofC. albicans-S.Typhimurium coinfection, as well as with biofilm formation byC. albicans. We confirmed that SopB translocated to fungal filaments through SipB during coinfection. Using quantitative real-time PCR assays, we found that theCandidasupernatant upregulated theS.Typhimurium genes associated withC. albicanskilling (sopBandsipB). Interestingly, the sopBeffector negatively regulated the transcription ofCDC42, which is involved in fungal viability. Taken together, these results indicate that specific TTSS effectors, including SopB, play a critical role in bacterial-fungal interactions and are important toS.Typhimurium in order to selectively compete with fungal pathogens. These findings highlight a new role for TTSS ofS.Typhimurium in the intestinal tract and may further explain the evolution and maintenance of these traits.

scholarly journals The Type III Secretion System Effector SeoC of Salmonella enterica subsp. salamae and S. enterica subsp. arizonae ADP-Ribosylates Src and Inhibits Opsonophagocytosis

2016 ◽  
Vol 84 (12) ◽  
pp. 3618-3628 ◽  
Author(s):  
Dominic J. Pollard ◽  
Joanna C. Young ◽  
Valentina Covarelli ◽  
Silvia Herrera-León ◽  
Thomas R. Connor ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Draft Genome ◽  
Ectopic Expression ◽  
Host Cells ◽  
Mammalian Host ◽  
Dependent Manner ◽  
Secretion Systems ◽  
Content Type ◽  
Type Iii

Salmonellaspecies utilize type III secretion systems (T3SSs) to translocate effectors into the cytosol of mammalian host cells, subverting cell signaling and facilitating the onset of gastroenteritis. In this study, we compared a draft genome assembly ofSalmonella entericasubsp.salamaestrain 3588/07 against the genomes ofS. entericasubsp.entericaserovar Typhimurium strain LT2 andSalmonella bongoristrain 12419.S. entericasubsp.salamaeencodes theSalmonellapathogenicity island 1 (SPI-1), SPI-2, and the locus of enterocyte effacement (LEE) T3SSs. Though several keyS. Typhimurium effector genes are missing (e.g.,avrA,sopB, andsseL),S. entericasubsp.salamaeinvades HeLa cells and contains homologues ofS. bongori sboKandsboC, which we namedseoC. SboC and SeoC are homologues of EspJ from enteropathogenic and enterohemorrhagicEscherichia coli(EPEC and EHEC, respectively), which inhibit Src kinase-dependent phagocytosis by ADP-ribosylation. By screening 73 clinical and environmentalSalmonellaisolates, we identified EspJ homologues inS. bongori,S. entericasubsp.salamae, andSalmonella entericasubsp.arizonae. The β-lactamase TEM-1 reporter system showed that SeoC is translocated by the SPI-1 T3SS. All theSalmonellaSeoC/SboC homologues ADP-ribosylate Src E310in vitro. Ectopic expression of SeoC/SboC inhibited phagocytosis of IgG-opsonized beads into Cos-7 cells stably expressing green fluorescent protein (GFP)-FcγRIIa. Concurrently,S. entericasubsp.salamaeinfection of J774.A1 macrophages inhibited phagocytosis of beads, in aseoC-dependent manner. These results show thatS. bongori,S. entericasubsp.salamae, andS. entericasubsp.arizonaeshare features of the infection strategy of extracellular pathogens EPEC and EHEC and shed light on the complexities of the T3SS effector repertoires ofEnterobacteriaceae.

scholarly journals Identification of Mammalian Proteins That Collaborate with Type III Secretion System Function: Involvement of a Chemokine Receptor in Supporting Translocon Activity

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Kerri-Lynn Sheahan ◽  
Ralph R. Isberg
Keyword(s):  
Host Cell ◽  
Type Iii Secretion ◽  
Pore Formation ◽  
Yersinia Pseudotuberculosis ◽  
Secretion System ◽  
Host Cells ◽  
Secretion Systems ◽  
Gram Negative ◽  
Content Type ◽  
Type Iii

ABSTRACTThe type III secretion system (T3SS) is a highly conserved protein delivery system found in multiple Gram-negative pathogens, includingYersinia pseudotuberculosis. Most studies of Yersinia species type III intoxication of host cells have focused on the bacterial determinants that promote assembly and function of the secretion system. In this study, we performed a pooled RNA interference (RNAi) screen to identify mammalian host proteins required for the cytotoxic effects associated with the Yersinia translocated substrate YopE, a GTPase-activating protein (GAP) that inactivates the small Rho GTPases. Cell populations were positively selected for short hairpin RNAs (shRNAs) that interfere with YopE activity using a combination of fluorescence resonance energy transfer (FRET) and flow cytometry, and the degree of enrichment was determined by deep sequencing. Analysis of the candidates identified by the enrichment process revealed that many were important for the initial step of Y. pseudotuberculosis T3SS function, YopB/D pore formation. These candidates included shRNA that depleted downstream effectors of RhoA signaling, coated pit formation, and receptors involved in cell signaling, including the chemokine receptor CCR5 (chemokine [C-C motif] receptor 5). Depletion of CCR5 in 293T cells yielded a defect in YopB/D pore formation and effector translocation, while both phenotypes could be complemented by overexpression of CCR5 protein. Yop effector translocation was also decreased in isolated primary phagocytic cells from aCcr5−/−knockout mouse. We postulate that CCR5 acts to promote translocation by modulating cytoskeletal activities necessary for proper assembly of the YopB/D translocation pore. Overall, this study presents a new approach to investigating the contribution of the host cell to T3SS in Y. pseudotuberculosis.IMPORTANCEMany Gram-negative bacteria require type III secretion systems (T3SS) for host survival, making these highly specialized secretion systems good targets for antimicrobial agents. After the bacterium binds to host cells, T3SS deposit proteins into the cytosol of host cells through a needle-like appendage and a protein translocon channel. Translocation of proteins via this system is highly regulated, and the contribution of the host cell in promoting assembly and insertion of the channel into the plasma membrane, folding of the bacterial proteins, and trafficking of these substrates are all poorly characterized events. In this study, we identified host cell proteins important for activity of YopE, aYersinia pseudotuberculosisT3SS-delivered protein. The results demonstrate that insertion and assembly of the translocon are complex processes, requiring a variety of membrane trafficking and cytoskeletal processes, as well as a surprising role for cell surface signaling molecules in supporting proper function.

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