YopD of <i>Yersinia pseudotuberculosis</i> is translocated into the cytosol of HeLa epithelial cells: evidence of a structural domain necessary for translocation

Francis, Matthew S.; Wolf‐Watz, Hans

doi:10.1046/j.1365-2958.1998.00973.x

Cited by 121 publications

(173 citation statements)

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(172 reference statements)

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“…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 & Straley, 1998). However, this phenotype depends on a complex between YopD and LcrH (Anderson et al, 2002;Francis et al, 2001), a specialized type III secretion chaperone that ensures the pre-secretory stabilization and efficient secretion of both YopB and YopD (Francis et al, 2000;Neyt & Cornelis, 1999b;Wattiau et al, 1994).…”

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

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“…YopK is a translocated effector that regulates the translocation of other Yersinia Yops (42,84). YopK deficiency results in significantly attenuated infection in vivo, which was initially surprising given that YopK-deficient Yersinia translocate an increased amount of virulence factors into target cells (36,76,85,86).…”

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“…YopB and YopD are both integral transmembrane proteins and form the pore, or translocon complex, through which other Yops are injected into the host cell. Both YopB and YopD are required for functional translocation of the secreted effector Yops (42)(43)(44). In addition to being required for translocation of other Yops, YopB and YopD are also injected into host cells (42,45,46).…”

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“…Both YopB and YopD are required for functional translocation of the secreted effector Yops (42)(43)(44). In addition to being required for translocation of other Yops, YopB and YopD are also injected into host cells (42,45,46). Critically, in the absence of YopK, both YopB and YopD are hypertranslocated, resulting in the activation of both canonical and noncanonical inflammasomes (42,45,46).…”

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“…In addition to being required for translocation of other Yops, YopB and YopD are also injected into host cells (42,45,46). Critically, in the absence of YopK, both YopB and YopD are hypertranslocated, resulting in the activation of both canonical and noncanonical inflammasomes (42,45,46). Moreover, we previously found that inflammasome activation by the yopK mutant is abrogated by point mutations of the YopB/-D-specific chaperone LcrH that eliminate hypertranslocation of YopB/-D but do not affect the translocation of other Yops (46).…”

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Guanylate Binding Proteins Regulate Inflammasome Activation in Response to Hyperinjected Yersinia Translocon Components

et al. 2017

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Gram-negative bacterial pathogens utilize virulence-associated secretion systems to inject, or translocate, effector proteins into host cells to manipulate cellular processes and promote bacterial replication. However, translocated bacterial products are sensed by nucleotide binding domain and leucine-rich repeat-containing proteins (NLRs), which trigger the formation of a multiprotein complex called the inflammasome, leading to secretion of interleukin-1 (IL-1) family cytokines, pyroptosis, and control of pathogen replication. Pathogenic Yersinia bacteria inject effector proteins termed Yops, as well as pore-forming proteins that comprise the translocon itself, into target cells. The Yersinia translocation regulatory protein YopK promotes bacterial virulence by limiting hyperinjection of the translocon proteins YopD and YopB into cells, thereby limiting cellular detection of Yersinia virulence activity. How hyperinjection of translocon proteins leads to inflammasome activation is currently unknown. We found that translocated YopB and YopD colocalized with the late endosomal/lysosomal protein LAMP1 and that the frequency of YopD and LAMP1 association correlated with the level of caspase-1 activation in individual cells. We also observed colocalization between YopD and Galectin-3, an indicator of endosomal membrane damage. Intriguingly, YopK limited the colocalization of Galectin-3 with YopD, suggesting that YopK limits the induction or sensing of endosomal membrane damage by components of the type III secretion system (T3SS) translocon. Furthermore, guanylate binding proteins (GBPs) encoded on chromosome 3 (Gbp Chr3 ), which respond to pathogen-induced damage or alteration of host membranes, were necessary for inflammasome activation in response to hyperinjected YopB/-D. Our findings indicate that lysosomal damage by Yersinia translocon proteins promotes inflammasome activation and implicate GBPs as key regulators of this process.

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Yersinia enterocolitica-mediated translocation of defined fusion proteins to the cytosol of mammalian cells results in peptide-specific MHC class I-restricted antigen presentation

Rüssmann

Weissmüller

Geginat³

et al. 2000

Eur. J. Immunol.

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YopD of Yersinia pseudotuberculosis is translocated into the cytosol of HeLa epithelial cells: evidence of a structural domain necessary for translocation

Cited by 121 publications

References 74 publications

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

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

Guanylate Binding Proteins Regulate Inflammasome Activation in Response to Hyperinjected Yersinia Translocon Components

Yersinia enterocolitica-mediated translocation of defined fusion proteins to the cytosol of mammalian cells results in peptide-specific MHC class I-restricted antigen presentation

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