Post-translational regulation of Lcr plasmid-mediated peptides in pesticinogenic Yersinia pestis

Sample, Allen K.; Brubaker, Robert R.

doi:10.1016/0882-4010(87)90057-x

Cited by 37 publications

(47 citation statements)

References 33 publications

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“…Another difference in secretion is that plague bacilli fail to express Yops in vitro in a Ca 2ϩ -deficient environment found to promote excellent expression by enteropathogenic species (98). This difference is due to the presence of Pla in Y. pestis, which catalyzes the prompt posttranslational degradation of Yops but does not destroy LcrV (59,85,95). This finding does not mean that Yops are redundant in plague bacilli; indeed, mutational loss of any such effector other than YopJ causes significant loss of virulence (9,75,97).…”

Section: Integration Of Traditionsmentioning

confidence: 99%

Interleukin-10 and Inhibition of Innate Immunity to Yersiniae: Roles of Yops and LcrV (V Antigen)

2003

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Section: Integration Of Traditionsmentioning

confidence: 99%

Interleukin-10 and Inhibition of Innate Immunity to Yersiniae: Roles of Yops and LcrV (V Antigen)

2003

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“…Pla, a multifunctional outer membrane protease, is believed to contribute to the highly invasive nature of Y. pestis (45,68). Notably, Pla shares homology with other proteolytic plasminogen activators, and in addition to plasminogen, the Pla protease cleaves complement component C3 (63,70), suggesting a role for Pla in the host bloodstream. However, previous experiments with pla deletion mutants have shown that the virulence role of Pla may be strain dependent and related to the route of infection (79).…”

Section: Differential Protein Expression Following Change From 26°cmentioning

confidence: 99%

Proteomic Characterization ofYersinia pestisVirulence

et al. 2005

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The Yersinia pestis proteome was studied as a function of temperature and calcium by two-dimensional differential gel electrophoresis. Over 4,100 individual protein spots were detected, of which hundreds were differentially expressed. A total of 43 differentially expressed protein spots, representing 24 unique proteins, were identified by mass spectrometry. Differences in expression were observed for several virulence-associated factors, including catalase-peroxidase (KatY), murine toxin (Ymt), plasminogen activator (Pla), and F1 capsule antigen (Caf1), as well as several putative virulence factors and membrane-bound and metabolic proteins. Differentially expressed proteins not previously reported to contribute to virulence are candidates for more detailed mechanistic studies, representing potential new virulence determinants.Yersinia pestis, the etiological agent of plague, is a gram-negative bacterium that is both a natural environmental pathogen and a biothreat agent (4,8,32). Early studies of Yersinia physiology uncovered the low calcium response (LCR), whereby bacterial cultures grown in rich medium at an elevated temperature (37°C) exhibit a growth defect upon chelation of calcium ions. The growth arrest was shown to be a result of one of the two type III secretion systems (TTSSs) in Y. pestis, the Ysc TTSS, and is responsible for the secretion of virulence factors known as Yersinia outer proteins, or Yops (21, 29; for a review, see reference 61). This TTSS can be activated in vitro and virulence factors can be released into the medium when Y. pestis is grown at 37°C with submillimolar calcium (for a review, see reference 16). Upon interaction with the host, the TTSS enables virulence factors to enter the host cell through a specialized apparatus, the injectisome (15). Once inside the host cell, Yops affect a variety of host pathways, with detectable expression changes in the pathogen as well as the host (14,52,82).The Y. pestis proteome was previously examined using twodimensional electrophoresis (57,60,71,72). These studies demonstrated that virulence factors were not induced at 26°C or 37°C in the presence of calcium concentrations similar to that found in mammalian plasma (2.5 mM) (71). More recently, the introduction of two-dimensional differential gel electrophoresis (2-D DIGE) has significantly improved the quality of gel-based proteomics through fluorescence-based multiplex analyses providing relative quantitation of expression differences and improved gel-to-gel comparisons (75). Several examples of 2-D DIGE bacterial proteomics have been reported (23), including characterizations of the gram-negative bacterium Escherichia coli (1, 76, 81). Here we report the characterization of the soluble cell-associated proteome of Y. pestis as a function of temperature and calcium, which were used to effect virulence induction. Differentially expressed proteins include virulence-associated factors, membrane-bound proteins, metabolic and housekeeping proteins, and potential new virulence determinants.Bacterial ...

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“…Limited evidence suggests that anti-V antibodies may neutralize an antihost function of LcrV in the extracellular environment. LcrV is secreted from yersiniae (49) and accumulates outside the cells even when Pla is present (7,57). Moreover, the V antigen has never been found to associate with the bacterial surface as do Yops in enteropathogenic yersiniae or in Pla Ϫ Y. pestis (58).…”

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confidence: 99%

“…In Y. pestis, Yops are attacked by a plasminogen activator protease (Pla), encoded on a species-specific ca. 9.5-kbp pPCP1 plasmid and, as a result, do not accumulate on the bacterial surface in vitro (49,(54)(55)(56).…”

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confidence: 99%

Differential effects of deletions in lcrV on secretion of V antigen, regulation of the low-Ca2+ response, and virulence of Yersinia pestis

1995

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The Yersinia pestis V antigen is necessary for full induction of low-calcium response (LCR) stimulon virulence gene transcription, and it also is a secreted protein believed to have a direct antihost function. We made four nonpolar deletions in lcrV of Y. pestis to determine if secretion, regulation, and virulence functions could be localized within the V antigen (LcrV). Deletion of amino acids 25 to 40 caused secretion of LcrV to be decreased in efficiency; however, removal of residues 108 to 125 essentially abolished LcrV secretion. Neither mutation had a significant effect on LCR regulation. This showed that LcrV does not have to be secreted to have its regulatory effect and that the internal structure of V antigen is necessary for its secretion. Both mutants were avirulent in mice, showing that the regulatory effect of LcrV could be separated genetically from its virulence role and raising the possibility that residues 25 to 40 are essential for the virulence function. This study provides the best genetic evidence available that LcrV per se is necessary for the virulence of Y. pestis. The repressed LCR phenotype of a mutant lacking amino acids 188 to 207 of LcrV raised the possibility that the deleted region is necessary for regulation of LCR induction; however, this mutant LcrV was weakly expressed and may not have been present in sufficient amounts to have its regulatory effect. In double mutants containing this mutant lcrV and also lacking expression of known LCR negative regulators (LcrG, LcrE, and LcrH), full induction of the LCR occurred in the absence of functional LcrV, indicating that LcrV promotes induction not as an activator per se but rather by inhibiting negative regulators.

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Post-translational regulation of Lcr plasmid-mediated peptides in pesticinogenic Yersinia pestis

Cited by 37 publications

References 33 publications

Interleukin-10 and Inhibition of Innate Immunity to Yersiniae: Roles of Yops and LcrV (V Antigen)

Interleukin-10 and Inhibition of Innate Immunity to Yersiniae: Roles of Yops and LcrV (V Antigen)

Proteomic Characterization ofYersinia pestisVirulence

Differential effects of deletions in lcrV on secretion of V antigen, regulation of the low-Ca2+ response, and virulence of Yersinia pestis

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