Bile salt receptor complex activates a pathogenic type III secretion system

Li, Peng; Rivera-Cancel, Giomar; Kinch, Lisa N.; Salomon, Dor; Tomchick, Diana R.; Grishin, Nick V.; Orth, Kim

doi:10.7554/elife.15718

Cited by 71 publications

(128 citation statements)

References 64 publications

(90 reference statements)

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“…Oligomerization of the N‐terminal DNA‐binding domain of VtrA enhances its DNA‐binding activity, thus probably facilitating the transcriptional regulatory activity of VtrA. V. parahaemolyticus T3SS2 regulator C (VtrC), a protein that is cotranscribed with VtrA, is also required for the transcriptional activation of the genes that encode T3SS2 . VtrC forms a complex with the C‐terminal domain of VtrA (VtrA/VtrC), which might stabilize VtrA in V. parahaemolyticus .…”

Section: Regulation Of T3ss2 Gene Expressionmentioning

confidence: 99%

“…Instead, bile induces VtrA oligomerization, causing enhanced binding of VtrA to the promoter region of vtrB . Cocrystallization of the periplasmic domain complex formed by VtrA and VtrC in the presence of taurodeoxycholate revealed that eight β‐strands of VtrC and one β‐strand of VtrA form a β‐barrel with a hydrophobic inner chamber that binds taurodeoxycholate . Although it is uncertain how the binding of bile acids to VtrA/VtrC affects the transcriptional regulatory activity of VtrA, these findings suggest that VtrA/VtrC senses bile, leading to the activation of the DNA‐binding domain of VtrA, probably through its oligomerization.…”

Section: Host‐derived Inducers For T3ss2 Gene Expressionmentioning

confidence: 99%

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Advances on Vibrio parahaemolyticus research in the postgenomic era

Matsuda

Hiyoshi

Tandhavanant

et al. 2020

Microbiology and Immunology

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Vibrio parahaemolyticus is a leading cause of seafood‐borne bacterial gastroenteritis in humans. Since its discovery in 1950, this bacterium has been isolated in widespread outbreaks and in sporadic cases of gastroenteritis worldwide. Although the exotoxin, thermostable direct hemolysin, had been the focus of extensive research on the pathogenicity of V. parahaemolyticus, the whole‐genome sequencing of a clinical isolate, RIMD2210633 strain, was a breakthrough in this field. The possession of two sets of gene clusters for type III secretion systems (T3SS1 and T3SS2) was unveiled by that genome project. T3SS is a protein export apparatus that delivers bacterial proteins, called effectors, directly into the host's cytosol, to disrupt host cell function. The subsequent studies have established that T3SS2, which is encoded in an 80 kb pathogenicity island called V. parahaemolyticus pathogenicity island (Vp‐PAI), is closely related to enteropathogenicity. Recent functional analyses of Vp‐PAI‐encoded genes revealed the sophisticated mechanisms in V. parahaemolyticus for sensing the intestinal environment and host cell contact, and a dozen T3SS2‐exported proteins encoded in Vp‐PAI. In this review, we summarize recent advances in V. parahaemolyticus research regarding the control of the expression of Vp‐PAI‐encoded genes, structural components and the secretory regulation of T3SS2, and the biological activities of T3SS2‐exported effectors. Thus, Vp‐PAI‐encoded T3SS2 becomes an important key in the postgenomic era to shed light on the enteropathogenic mechanism of V. parahaemolyticus.

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Section: Regulation Of T3ss2 Gene Expressionmentioning

confidence: 99%

Section: Host‐derived Inducers For T3ss2 Gene Expressionmentioning

confidence: 99%

Advances on Vibrio parahaemolyticus research in the postgenomic era

Matsuda

Hiyoshi

Tandhavanant

et al. 2020

Microbiology and Immunology

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show abstract

“…Analysis of the crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer revealed that VtrA and VtrC form a protein complex on the surface of the outer membrane creating a barrel‐like structure that binds to bile salts and induces V . parahaemolyticus to secrete toxins (Li et al, ).…”

Section: Introductionmentioning

confidence: 99%

The bile salt sodium taurocholate inducesCampylobacter jejuniouter membrane vesicle production and increases OMV-associated proteolytic activity

Elmi

Dorey

Watson

et al. 2017

Cellular Microbiology

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Campylobacter jejuni, the leading cause of bacterial acute gastroenteritis worldwide, secretes an arsenal of virulence-associated proteins within outer membrane vesicles (OMVs). C. jejuni OMVs contain three serine proteases (HtrA, Cj0511, and Cj1365c) that cleave the intestinal epithelial cell (IEC) tight and adherens junction proteins occludin and E-cadherin, promoting enhanced C. jejuni adhesion to and invasion of IECs. C. jejuni OMVs also induce IECs innate immune responses. The bile salt sodium taurocholate (ST) is sensed as a host signal to coordinate the activation of virulence-associated genes in the enteric pathogen Vibrio cholerae. In this study, the effect of ST on C. jejuni OMVs was investigated. Physiological concentrations of ST do not have an inhibitory effect on C. jejuni growth until the early stationary phase. Coculture of C. jejuni with 0.1% or 0.2% (w/v) ST stimulates OMV production, increasing both lipid and protein concentrations. C. jejuni ST-OMVs possess increased proteolytic activity and exhibit a different protein profile compared to OMVs isolated in the absence of ST. ST-OMVs exhibit enhanced cytotoxicity and immunogenicity to T84 IECs and enhanced killing of Galleria mellonella larvae. ST increases the level of mRNA transcripts of the OMVs-associated serine protease genes and the cdtABC operon that encodes the cytolethal distending toxin. Coculture with ST significantly enhances the OMVs-induced cleavage of E-cadherin and occludin. C. jejuni OMVs also cleave the major endoplasmic reticulum chaperone protein BiP/GRP78 and this activity is associated with the Cj1365c protease. These data suggest that C. jejuni responds to the presence of physiological concentrations of the bile salt ST that increases OMV production and the synthesis of virulence-associated factors that are secreted within the OMVs. We propose that these events contribute to pathogenesis.

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“…Growth in the presence of bile salts allowed for induction of T3SS2 [11, 12]. Mammalian host cells were subsequently infected with CAB2 strains at a multiplicity of infection (MOI) of 10 using culture medium devoid of antibiotics (infection medium).…”

Section: Methodsmentioning

confidence: 99%

T3SS effector VopL inhibits the host ROS response, promoting the intracellular survival of Vibrio parahaemolyticus

Santos¹,

Salomon²,

Orth³

2017

PLoS Pathog

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The production of antimicrobial reactive oxygen species by the nicotinamide dinucleotide phosphate (NADPH) oxidase complex is an important mechanism for control of invading pathogens. Herein, we show that the gastrointestinal pathogen Vibrio parahaemolyticus counteracts reactive oxygen species (ROS) production using the Type III Secretion System 2 (T3SS2) effector VopL. In the absence of VopL, intracellular V. parahaemolyticus undergoes ROS-dependent filamentation, with concurrent limited growth. During infection, VopL assembles actin into non-functional filaments resulting in a dysfunctional actin cytoskeleton that can no longer mediate the assembly of the NADPH oxidase at the cell membrane, thereby limiting ROS production. This is the first example of how a T3SS2 effector contributes to the intracellular survival of V. parahaemolyticus, supporting the establishment of a protective intracellular replicative niche.

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Bile salt receptor complex activates a pathogenic type III secretion system

Cited by 71 publications

References 64 publications

Advances on Vibrio parahaemolyticus research in the postgenomic era

Advances on Vibrio parahaemolyticus research in the postgenomic era

The bile salt sodium taurocholate inducesCampylobacter jejuniouter membrane vesicle production and increases OMV-associated proteolytic activity

T3SS effector VopL inhibits the host ROS response, promoting the intracellular survival of Vibrio parahaemolyticus

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