Modulation of Virulence Factor Expression by Pathogen Target Cell Contact

Pettersson, Jonas; Nordfelth, Roland; Dubinina, E. E.; Bergman, Tomas; Gustafsson, Mikael; Magnusson, Karl‐Eric; Wolf‐Watz, Hans

doi:10.1126/science.273.5279.1231

Cited by 373 publications

(387 citation statements)

References 23 publications

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“…From these observations, they suggested that LcrQ could be the effector of the feedback regulation mechanism. Recently, they confirmed that LcrQ is rapidly released when bacteria are shifted from a medium containing 2.5 mM Ca 2þ (non-permissive for Yop secretion) to a medium containing a Ca 2þ chelator (permissive for Yop secretion) (Pettersson et al, 1996). They also observed derepression of Yop synthesis in a yscS -lcrQ double mutant, compared with a single yscS mutant.…”

Section: Introductionmentioning

confidence: 85%

YscM1 and YscM2, two Yersinia enterocolitica proteins causing downregulation of yop transcription

Stainier

Iriarte

Cornelis

1997

Molecular Microbiology

111

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SummarySynthesis of the Yop proteins by yersiniae is downregulated when secretion is prevented by closure or destruction of the contact (type III) secretion channel. In Yersinia pseudotuberculosis, a mutation in the lcrQ gene, encoding a secreted protein, reduces this feedback inhibition mechanism. Surprisingly, mutation in the yscM gene, the lcrQ homologue in Y. enterocolitica, does not lead to the same deregulated phenotype. In this paper, we addressed the question of this discrepancy. We found a new gene on the Y. enterocolitica pYV plasmid that encodes a protein with 57% identity to YscM (now called YscM1). Overexpression of this gene, called yscM2, like overexpression of lcrQ and yscM1, blocked Yop secretion. A double yscM1, yscM2 mutant had the same phenotype as that of the lcrQ mutant. The discrepancy can thus be explained by the existence of two functionally equivalent copies of yscM in Y. enterocolitica. Overexpression of yscM1 drastically reduced the expression of a yopH-cat reporter gene when tested in a pYV þ background. However, no effect could be observed in the absence of a pYV plasmid, indicating that YscM1 does not act directly as a transcriptional repressor or as an anti-VirF factor. We have also ruled out that YscM acts by obstructing the secretion channel.

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Section: Introductionmentioning

confidence: 85%

YscM1 and YscM2, two Yersinia enterocolitica proteins causing downregulation of yop transcription

Stainier

Iriarte

Cornelis

1997

Molecular Microbiology

111

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“…The first observation of gene expression being coupled to secretory activity in the injectisome systems was made in Yersinia pseudotuberculosis [35]. Each of the three pathogenic species of Yersinia (Y. entereocolitica, Y. pestis, Y. pseudotuberculosis) utilize the injectisome to translocate Yop effector proteins into host cells.…”

Section: Yersinia Spmentioning

confidence: 99%

“…Contact of Yersiniae with host cells also results in increased yop transcription through an undefined mechanism [35]. Transcription in the Yersinia injectisome system is controlled by an AraC-like protein (LcrF/VirF).…”

Section: Yersinia Spmentioning

confidence: 99%

Control of gene expression by type III secretory activity

Brutinel

Yahr

2008

Current Opinion in Microbiology

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SummaryThe bacterial flagellum and the highly related injectisome (or needle complex) are among the most complicated multi-protein structures found in Gram-negative microorganisms. The assembly of both structures is dependent upon a type III secretion system. An interesting regulatory feature unique to these systems is the coordination of gene expression with type III secretory activity. This means of regulation ensures that secretion substrates are expressed only when required during the assembly process or upon completion of the fully functional structure. Prominent within the regulatory scheme are secreted proteins and type III secretion chaperones that exert effects on gene expression at the transcriptional and post-transcriptional levels. Although the major structural components of the flagellum and injectisome systems are highly conserved, recent studies reveal diversity in the mechanisms used by secretion substrates and chaperones to control gene expression.

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“…The transcription of the yop genes is regulated by temperature and the transcriptional activator VirF plays a central role in this regulation (Cornelis et al, 1989). In addition, optimal yop expression requires contact with the eukaryotic target cell (Pettersson et al, 1996). This situation can be mimicked in vitro by growing the bacteria under Ca 2þ limitation.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, Yop secretion and yop expression are closely coupled. Although the mechanism of this feedback regulation is not very well understood, the product of the yscM gene (LcrQ) is implicated in this process by acting as a secretable negative regulator (Pettersson et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

The outer membrane component, YscC, of the Yop secretion machinery of Yersinia enterocolitica forms a ring‐shaped multimeric complex

Koster

Bitter

Cock

et al. 1997

Molecular Microbiology

212

217

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SummaryThe YscC protein of Yersinia enterocolitica is essential for the secretion of anti-host factors, called Yops, into the extracellular environment. It belongs to a family of outer membrane proteins, collectively designated secretins, that participate in a variety of transport processes. YscC has been shown to exist as a stable oligomeric complex in the outer membrane. The production of the YscC complex is regulated by temperature and is reduced in strains carrying mutations in the yscN-U operon or in the virG gene. The VirG lipoprotein was shown to be required for efficient targeting of the complex to the outer membrane. Electron microscopy revealed that purified YscC complexes form ring-shaped structures of Ϸ 20 nm with an apparent central pore. Because of the architecture of the multimer, YscC appears to represent a novel type of channel-forming proteins in the bacterial outer membrane.

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Modulation of Virulence Factor Expression by Pathogen Target Cell Contact

Cited by 373 publications

References 23 publications

YscM1 and YscM2, two Yersinia enterocolitica proteins causing downregulation of yop transcription

YscM1 and YscM2, two Yersinia enterocolitica proteins causing downregulation of yop transcription

Control of gene expression by type III secretory activity

The outer membrane component, YscC, of the Yop secretion machinery of Yersinia enterocolitica forms a ring‐shaped multimeric complex

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