Bile salt receptor complex activates a pathogenic type III secretion system.

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

doi:10.7554/elife.15718

Peng Li, Dor Salomon + Show 5 more

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https://doi.org/10.7554/elife.15718

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Abstract

Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered that Vibrio parahaemolyticus VtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment.

Highlights

Bile is an important component of the human gastrointestinal tract that plays a major role in the emulsification and solubilization of lipids (Begley et al, 2005)
VtrC is conserved in various bacterial species with VtrA-like genes and encodes a predicted transmembrane protein vtrC is a previously uncharacterized gene in V. parahaemolyticus that is located directly downstream of vtrA (Figure 1A)
Bile sensing plays a significant role in human infection caused by various enteric bacterial pathogens (Begley et al, 2005)

Summary

Introduction

Bile is an important component of the human gastrointestinal tract that plays a major role in the emulsification and solubilization of lipids (Begley et al, 2005). Bile has important effects on the pathogenicity of Vibrio species, as observed in multiple studies with pathogenic strains of V. cholerae and V. parahaemolyticus (Gupta and Chowdhury, 1997; Schuhmacher and Klose, 1999; Krukonis and DiRita, 2003; Faruque et al, 1998). V. cholerae produces two major virulence factors during infection, cholera toxin (CT) and toxin-coregulated pilus (TCP), and these factors are repressed by ToxT in the presence of bile (Gupta and Chowdhury, 1997; Schuhmacher and Klose, 1999; Krukonis and DiRita, 2003; Faruque et al, 1998).

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