The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine (plos pathogens 2017, 13(1):e1006119)

報告日期: 2017/03/21
報告時間: 5:10/6:00
報告學生: 黃建銘(以英文報告)
講評老師: 鄧景浩
附件下載: 下載[1620-1487729269-1.pdf] 

The effector domain region of the Vibrio vulnificus MARTX toxin confers biphasicepithelial barrier disruption and is essentialfor systemic spread from the intestine

Hannah E. Gavin, Nike T. Beubier, Karla J. F. Satchell

PLoS Pathog (2017) 13(1): e1006119

Speaker: Jian-Ming Huang (黃建銘)           Time: 17:10~18:00, Mar. 21, 2017

Commentator: Dr. Ching-Hao Teng (鄧景浩 老師) Place: Room 602

Abstract:

         The bacterium Vibrio vulnificus, a species of Gram-negative, causes highly lethal infections in susceptible individuals exposed to contaminated water or seafood.  Human infected by V. vulnificus progresses to septic shock and multiorgan failure that this rise in bacterial loads in the liver and spleen may predict dissemination associated fatality. Previous study showed that the rtxA1 gene in the Vibrio vulnificus encodes a secreted multifunctional autoprocessing repeats-in-toxins (MARTX) toxin that is the dominant virulence factor for intestinal infection[1]. However, the mechanism is still unknown due to the 5206 a.a. MARTX toxin produced by V. vulnificus strain CMCP6 contains long regions of highly conserved tandem amino acid repeats at the N- and C-termini[2]. Therefore, the authors hypothesized that the MARTX toxin effector domain region is principal for pathogenesis of V. vulnificus. First, the authors used an intragastric mouse model to demonstrate that the effector domain region is required for bacterial virulence during intragastric infection. The MARTX effector domain region is vital for bacterial dissemination from the intestine; nevertheless, dissemination takes place in the absence of overt intestinal tissue pathology. Moreover, the authors employed an in vitro model of V. vulnificus interaction with polarized colonic epithelial cells to show that the MARTX effector domain region induces rapid host cell disruption and increased paracellular permeability prior to onset of cell lysis. In conclusion, the authors characterized the functional roles of MARTX toxin regions in V. vulnificus pathogenesis and virulence during infection. V. vulnificus bacteria expressing the MARTX holotoxin rapidly induce intestinal epithelial dysfunction and increase permeability and transmigration.

References:

  1. Jeong, H.-G. and K.J. Satchell, Additive function of Vibrio vulnificus MARTX Vv and VvhA cytolysins promotes rapid growth and epithelial tissue necrosis during intestinal infection. PLoS Pathog, 2012. 8(3): p. e1002581.
  2. Kim, Y.R., et al., Vibrio vulnificus RTX toxin kills host cells only after contact of the bacteria with host cells. Cellular microbiology, 2008. 10(4): p. 848-862.