<i>Yersinia enterocolitica</i>
            TyeA, an Intracellular Regulator of the Type III Machinery, Is Required for Specific Targeting of YopE, YopH, YopM, and YopN into the Cytosol of Eukaryotic Cells

Cheng, Luisa W.; Schneewind, Olaf

doi:10.1128/jb.182.11.3183-3190.2000

Cited by 70 publications

(108 citation statements)

References 42 publications

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“…Secreted antagonists regulate flagellar genes in Salmonella (36, 37) and T3SS loci in Pseudomonas aeruginosa (38), Yersinia spp. (39), Shigella (40), and other bacteria (41). A unique feature of btrA, however, is the extent and diversity of expression profiles it controls.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of type III secretion and virulence genes inBordetella pertussisandBordetella bronchisepticaby a secreted anti-σ factor

Ahuja

Shokeen

Cheng

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The BvgAS phosphorelay regulates ∼10% of the annotated genomes of Bordetella pertussis and Bordetella bronchiseptica and controls their infectious cycles. The hierarchical organization of the regulatory network allows the integration of contextual signals to control all or specific subsets of BvgAS-regulated genes. Here, we characterize a regulatory node involving a type III secretion system (T3SS)-exported protein, BtrA, and demonstrate its role in determining fundamental differences in T3SS phenotypes among Bordetella species. We show that BtrA binds and antagonizes BtrS, a BvgAS-regulated extracytoplasmic function (ECF) sigma factor, to couple the secretory activity of the T3SS apparatus to gene expression. In B. bronchiseptica, a remarkable spectrum of expression states can be resolved by manipulating btrA, encompassing over 80 BtrA-activated loci that include genes encoding toxins, adhesins, and other cell surface proteins, and over 200 BtrA-repressed genes that encode T3SS apparatus components, secretion substrates, the BteA effector, and numerous additional factors. In B. pertussis, BtrA retains activity as a BtrS antagonist and exerts tight negative control over T3SS genes. Most importantly, deletion of btrA in B. pertussis revealed T3SS-mediated, BteA-dependent cytotoxicity, which had previously eluded detection. This effect was observed in laboratory strains and in clinical isolates from a recent California pertussis epidemic. We propose that the BtrA-BtrS regulatory node determines subspecies-specific differences in T3SS expression among Bordetella species and that B. pertussis is capable of expressing a full range of T3SS-dependent phenotypes in the presence of appropriate contextual cues.virulence gene regulation | ECF sigma factor | T3SS | Bordetella | host adaptation

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Section: Discussionmentioning

confidence: 99%

Differential regulation of type III secretion and virulence genes inBordetella pertussisandBordetella bronchisepticaby a secreted anti-σ factor

Ahuja

Shokeen

Cheng

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…In vitro studies have implicated YopD in complexes with structural components including YopB (Hartland & Robins-Browne, 1998;Neyt & Cornelis, 1999b), LcrV (Sarker et al, 1998) and TyeA (Cheng & Schneewind, 2000;Iriarte et al, 1998), in addition to the customized chaperone LcrH (Francis et al, 2000;Wattiau et al, 1994) and the translocated YopE effector (Hartland & RobinsBrowne, 1998). Presumably, these interactions form the nucleus of functional translocation in Yersinia, such that PopD is deficient in one or more of these interactions.…”

Section: Discussionmentioning

confidence: 99%

Dissection of homologous translocon operons reveals a distinct role for YopD in type III secretion by Yersinia pseudotuberculosis

et al. 2003

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The homologous pcrGVHpopBD and lcrGVHyopBD translocase operons of Pseudomonas aeruginosa and pathogenic Yersinia spp., respectively, are responsible for the translocation of anti-host effectors into the cytosol of infected eukaryotic cells. In Yersinia, this operon is also required for yop-regulatory control. To probe for key molecular interactions during the infection process, the functional interchangeability of popB/yopB and popD/yopD was investigated. Secretion of PopB produced in trans in a DyopB null mutant of Yersinia was only observed when co-produced with its native chaperone PcrH, but this was sufficient to complement the yopB translocation defect. The Yersinia DyopD null mutant synthesized and secreted PopD even in the absence of native PcrH, yet this did not restore YopD-dependent yop-regulatory control or effector translocation. Thus, this suggests that key residues in YopD, which are not conserved in PopD, are essential for functional Yersinia type III secretion. INTRODUCTIONAll pathogenic Yersinia spp. encode a wide assortment of virulence determinants to establish a host infection (Revell & Miller, 2001). Significantly, a common plasmid-borne type III secretion system (TTSS) is essential for the fitness of Yersinia inside the host . This specialized virulence strategy links protein secretion across the bacterial envelope with translocation of anti-host virulence effectors through the plasma membrane of target eukaryotic cells. Effector proteins localized inside the target cell disable crucial signal transduction pathways, rendering the cell incapable of mounting an effective immune defence (Bliska, 2000; Fällman et al., 2002).The bacterial envelope component of the TTSSs of many plant-and animal-interacting bacteria resembles the flagella basal body, while a hollow needle-like protrusion extends from the bacterial surface through which effectors are believed to traverse (Blocker et al., 1999;Hoiczyk & Blobel, 2001;Jin & He, 2001;Kubori et al., 1998; Sekiya et al., 2001;Tamano et al., 2000). Furthermore, translocation into target cells by Yersinia requires the structural proteins LcrV, YopB and YopD. These proteins interact (Neyt & Cornelis, 1999b;Sarker et al., 1998) to presumably form a complex that facilitates pore formation in target cell membranes to allow entry of effector proteins into target cells (Bröms et al., 2003a; Holmström et al., 2001;Neyt & Cornelis, 1999a;Tardy et al., 1999). At odds with this dogma is a report suggesting that the needle component YscF is the sole requirement for effector translocation (Hoiczyk & Blobel, 2001). Clearly, the molecular mechanisms of this process are still unresolved. Interestingly, both LcrV and YopD also contribute to the control of type III substrate synthesis and secretion. Yop synthesis in LcrV-defective strains is significantly down-regulated (Bergman et al., 1991;Price et al., 1991;Skrzypek & Straley, 1995). On the other hand, Yersinia defective for YopD constitutively produce Yop proteins and LcrV (Francis & Wolf-Watz, 1998;Williams & Strale...

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“…One of the most successful strategies was adopted by Yersinia pestis, namely a type III secretion system that injects a set of paralyzing proteins directly into the cytoplasm of macrophages and lymphocytes that the bacterium encounters in the lymph nodes of infected individuals (3,4). As a result, the targeted cells become unable to respond, and the bacteria can multiply unopposed by the normal mechanisms of host defense.…”

Section: From the Infectious And Inflammatory Disease Center The Burmentioning

confidence: 99%

Inhibition of Yersinia Tyrosine Phosphatase by Furanyl Salicylate Compounds

Tautz

Bruckner

Sareth

et al. 2005

Journal of Biological Chemistry

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To avoid detection and targeting by the immune system, the plague-causing bacterium Yersinia pestis uses a type III secretion system to deliver a set of inhibitory proteins into the cytoplasm of immune cells. One of these proteins is an exceptionally active tyrosine phosphatase termed YopH, which paralyzes lymphocytes and macrophages by dephosphorylating critical tyrosine kinases and signal transduction molecules. Because Y. pestis strains lacking YopH are avirulent, we set out to develop small molecule inhibitors for YopH. We used a novel and cost-effective approach, in which leads from a chemical library screening were analyzed and computationally docked into the crystal structure of YopH. This resulted in the identification of a series of novel YopH inhibitors with nanomolar K i values, as well as the structural basis for inhibition. Our inhibitors lack the polar phosphate-mimicking moiety of rationally designed tyrosine phosphatase inhibitors, and they readily entered live cells and rescued them from YopHinduced tyrosine dephosphorylation, signaling paralysis, and cell death. These inhibitors may become useful for treating the lethal infection by Y. pestis.

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Yersinia enterocolitica TyeA, an Intracellular Regulator of the Type III Machinery, Is Required for Specific Targeting of YopE, YopH, YopM, and YopN into the Cytosol of Eukaryotic Cells

Cited by 70 publications

References 42 publications

Differential regulation of type III secretion and virulence genes inBordetella pertussisandBordetella bronchisepticaby a secreted anti-σ factor

Differential regulation of type III secretion and virulence genes inBordetella pertussisandBordetella bronchisepticaby a secreted anti-σ factor

Dissection of homologous translocon operons reveals a distinct role for YopD in type III secretion by Yersinia pseudotuberculosis

Inhibition of Yersinia Tyrosine Phosphatase by Furanyl Salicylate Compounds

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