LcrV Mutants That Abolish Yersinia Type III Injectisome Function

Ligtenberg, Katherine Given; Miller, Nathan C.; Mitchell, Andrew; Plano, Gregory V.; Schneewind, Olaf

doi:10.1128/jb.02021-12

Cited by 11 publications

(14 citation statements)

References 52 publications

(70 reference statements)

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“…Second, IpaB has been observed on the tip of needles as part of the tip complex (Ide et al, 2001; Olive et al, 2007; Veenendaal et al, 2007). Most recently, YopD has been detected in purified needle preparations in an LcrV-dependent manner (Ligtenberg et al, 2012). Furthermore, there is a direct correlation between the length of the needle, the distance between the bacteria and host cell, and the ability to inject Yops: the effect of changing the length of the surface adhesin YadA on Y. enterocolitica can be counteracted by changing the length of the needle (Mota et al, 2005).…”

Section: The Making Of An Injectisomementioning

confidence: 99%

Regulation of the Yersinia type III secretion system: traffic control

Dewoody¹,

Merritt²,

Marketon³

2013

Front. Cell. Inf. Microbio.

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Yersinia species, as well as many other Gram-negative pathogens, use a type III secretion system (T3SS) to translocate effector proteins from the bacterial cytoplasm to the host cytosol. This T3SS resembles a molecular syringe, with a needle-like shaft connected to a basal body structure, which spans the inner and outer bacterial membranes. The basal body of the injectisome shares a high degree of homology with the bacterial flagellum. Extending from the T3SS basal body is the needle, which is a polymer of a single protein, YscF. The distal end of the needle serves as a platform for the assembly of a tip complex composed of LcrV. Though never directly observed, prevailing models assume that LcrV assists in the insertion of the pore-forming proteins YopB and YopD into the host cell membrane. This completes a bridge between the bacterium and host cell to provide a continuous channel through which effectors are delivered. Significant effort has gone into understanding how the T3SS is assembled, how its substrates are recognized and how substrate delivery is controlled. Arguably the latter topic is the least understood; however, recent advances have provided new insight, and therefore, this review will focus primarily on summarizing the current state of knowledge regarding the control of substrate delivery by the T3SS. Specifically, we will discuss the roles of YopK, as well as YopN and YopE, which have long been linked to regulation of translocation. We also propose models whereby the YopK regulator communicates with the basal body of the T3SS to control translocation.

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Section: The Making Of An Injectisomementioning

confidence: 99%

Regulation of the Yersinia type III secretion system: traffic control

Dewoody¹,

Merritt²,

Marketon³

2013

Front. Cell. Inf. Microbio.

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“…YopD, but not YopB, has been found in purified needle preparations from Yersinia enterocolitica; however, its location on or within these needles has not be visualized by EM (10,11). While it has been speculated that the YopD in these complexes is due to secreted but insoluble YopD which copurifies with needles (11,12), recent work has also shown that YopD copurifies with LcrVcapped needles (10). YopB and YopD form a hetero-oligomeric pore in mammalian plasma membranes, termed the translocon, and are critical for the formation of a pore through which effector proteins are thought to travel (1,22).…”

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confidence: 99%

A Mutant with Aberrant Extracellular LcrV-YscF Interactions Fails To Form Pores and Translocate Yop Effector Proteins but Retains the Ability To Trigger Yop Secretion in Response to Host Cell Contact

et al. 2013

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The plasmid-encoded type three secretion system (TTSS) of Yersinia spp. is responsible for the delivery of effector proteins into cells of the innate immune system, where these effectors disrupt the target cells' activity. Successful translocation of effectors into mammalian cells requires Yersinia to both insert a translocon into the host cell membrane and sense contact with host cells. To probe the events necessary for translocation, we investigated protein-protein interactions among TTSS components of the needle-translocon complex using a chemical cross-linking-based approach. We detected extracellular protein complexes containing YscF, LcrV, and YopD that were dependent upon needle formation. The formation of these complexes was evaluated in a secretion-competent but translocation-defective mutant, the YscFD28AD46A strain (expressing YscF with the mutations D28A and D46A). We found that one of the YscF and most of the LcrV and YopD cross-linked complexes were nearly absent in this mutant. Furthermore, the YscFD28AD46A strain did not support YopB insertion into mammalian membranes, supporting the idea that the LcrV tip complex is required for YopB insertion and translocon formation. However, the YscFD28AD46A strain did secrete Yops in the presence of host cells, indicating that a translocation-competent tip complex is not required to sense contact with host cells to trigger Yop secretion. In conclusion, in the absence of cross-linkable LcrV-YscF interactions, translocon insertion is abolished, but Yersinia still retains the ability to sense cell contact.

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“…A mutant lacking aa 188–207 of LcrV reportedly displays LCR repression, suggesting that the deleted region is necessary for regulation of LCR induction . A recent study determined that the macromolecular structure of LcrV (the needle cap of the injection machinery, as explained later in this review) responds to LCR signals .…”

Section: Lcrv and Its Regulatory Role In Yop Secretionmentioning

confidence: 94%

V‐antigen homologs in pathogenic gram‐negative bacteria

Sawa

Katoh

Yanagimoto

2014

Microbiology and Immunology

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Gram-negative bacteria cause many types of infections in animals from fish and shrimps to humans. Bacteria use Type III secretion systems (TTSSs) to translocate their toxins directly into eukaryotic cells. The V-antigen is a multifunctional protein required for the TTSS in Yersinia and Pseudomonas aeruginosa. V-antigen vaccines and anti-V-antigen antisera confer protection against Yersinia or P. aeruginosa infections in animal models. The V-antigen forms a pentameric cap structure at the tip of the Type III secretory needle; this structure, which has evolved from the bacterial flagellar cap structure, is indispensable for toxin translocation. Various pathogenic gram-negative bacteria such as Photorhabdus luminescens, Vibrio spp., and Aeromonas spp. encode homologs of the V-antigen. Because the V-antigens of pathogenic gram-negative bacteria play a key role in toxin translocation, they are potential therapeutic targets for combatting bacterial virulence. In the USA and Europe, these vaccines and specific antibodies against V-antigens are in clinical trials investigating the treatment of Yersinia or P. aeruginosa infections. Pathogenic gram-negative bacteria are of great interest because of their ability to infect fish and shrimp farms, their potential for exploitation in biological terrorism attacks, and their ability to cause opportunistic infections in humans. Thus, elucidation of the roles of the V-antigen in the TTSS and mechanisms by which these functions can be blocked is critical to facilitating the development of improved anti-V-antigen strategies.

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LcrV Mutants That Abolish Yersinia Type III Injectisome Function

Cited by 11 publications

References 52 publications

Regulation of the Yersinia type III secretion system: traffic control

Regulation of the Yersinia type III secretion system: traffic control

A Mutant with Aberrant Extracellular LcrV-YscF Interactions Fails To Form Pores and Translocate Yop Effector Proteins but Retains the Ability To Trigger Yop Secretion in Response to Host Cell Contact

V‐antigen homologs in pathogenic gram‐negative bacteria

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