Large-Scale Screening of Human B-Lymphoblastoid Cell Lines Reveals Super Sensitive and Completely Resistant lines to E. coli Shiga Toxin 2
Abstract:
Diarrheal disease R and D is a top priority of the US Military. These diseases can severely hamper and disrupt mission operations, especially in deployment areas where the outbreaks are common. Among the causative agents of diarrheal disease are certain toxigenic strains of such bacteria as Escherichia coli, Shigella dysenteriae, and Campylobacter jejuni. The protein exotoxins produced by them are the central players in the virulence and disease pathogenesis of their respective strains. Among these toxins are the shigatoxins. This toxin family comprises the prototypic shigatoxin produced by S.dysenteriae and shigatoxin 1 (STx1) and shigatoxin 2 (STx2) produced by shigatoxigenic strains of E.coli. These strains include the highly virulent enterohemorrhagic E. coli strains such as 0157:H7. STx1and STx2 are crucial for the infectious pathogenesis, including hemorrhagic colitis and hemolyticuremic syndrome, which can be fatal. However, STx2 has a notable significance because it more frequently associates with the diarrheal disease severity, including hemorrhagic colitis and hemolyticuremic syndrome. Human susceptibility to the shigatoxigenic virulent strains and the ensuing pathogenesis is quite variable. Susceptibility of various cells and tissues to shigatoxins is also variable. The ultimate causal factors that account for this variability are genetic. The overall objective of the work reported here was to ascertain differences in cellular sensitivity or resistance to STx2.