Tale of Two Hosts: Vibrio parahaemolyticus Toxicity Against Human and Shrimp
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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 (T3SS2) 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. Acute hepatopancreatic necrosis disease (AHPND) is a newly emerging shrimp disease that has generated severe damage to the global shrimp industry. AHPND is caused by toxic strains of Vibrio paraehaemolyticus that have acquired a "selfish plasmid" encoding the deadly binary toxins PirAvp/PirBvp. To better understand the genetic features of AHPND causing Vibrio paraehaemolyticus, we conducted a comparative analysis using the genome sequences of the clinical isolate RIMD2210633, environmental non-AHPND and toxic AHPND isolates of Vibrio paraehaemolyticus. Our studies discovered a distinguishing feature that a virulent Type VI Secretions System (T6SS1), like that in RIMD2210633, is present in all of the AHPND but none of the non-AHPND strains. This T6SS1 is potentially conserved in these virulent strains because of its anti-bacterial activities to compete against other commensal bacteria during host infection.