As the Worm Turns

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http://www.genome.duke.edu/genomelife/glarchive/issue10/aballay

 

 

As the Worm Turns

 

Aballay Studies Pathogenesis in Nematode

 

 

Alejandro Aballay

 

 

Assistant Professor of Molecular Genetics and Microbiology Alejandro

Aballay spends a lot of time with some fairly undesirable—and

hard-to-pronounce—company: Pseudomonas aeruginosa and Salmonella

enterica for starters. Each is a potentially nasty pathogen.

Pseudomonas infects the respiratory tracts of cystic fibrosis patients

and also preys upon cancer and burn victims. It is remarkably adept at

causing problems for a broad range of hosts and their environments:

water, soil, plants and animals. One form of Salmonella is the

causative agent in typhus, while others can cause human

gastroenteritis (salmonellosis).

 

In search of an animal model to better understand this infectious

process, what Aballay and others (including his former mentor at

Harvard, Fred Ausubel) wanted to find out was whether these bugs were

also capable of infecting the nematode C. elegans . Because

Pseudomonas is such a broad-host-range pathogen, its ability to infect

the worm was not considered to be much of a litmus test. This prompted

Aballay to see if Salmonella could infect C. elegans. " Salmonella is

still a broad-host-range pathogen, but not as broad as Pseudomonas, "

he says. " We found we could indeed infect C. elegans with Salmonella. "

Remarkably, Salmonella infection of worms looks quite similar to the

same infection in mammals. " That's a real advantage, " says Aballay,

" since there are no good mammalian models to understand salmonellosis. "

 

How does Salmonella kill the worm? Aballay found that specific

virulence factors were required for the job—the pathogen injects them

into host cells, thereby altering signaling pathways in C. elegans,

and from there things quickly go downhill for the worm. Aballay's

group determined that the virulence factors (also called effector

proteins) diminish the innate immunity of the host and, in doing so,

render the host animals hypersusceptible to infection. By carrying out

a genetic screen of a Salmonella mutant library, Aballay's lab

identified a number of both novel and previously described virulence

factors. Their work appears in the June 8 issue of Current Biology.

 

Aballay's lab is abuzz with other projects. One involves determining

the function of a class of genes that mediate programmed cell death

and are necessary to fight Salmonella infection. His group is also

screening an RNA interference library (see article in this issue) for

genes involved in innate immunity and collecting comparative genomics

data on innate immunity genes. He points out that studying innate

immunity in the worm has only been done for five or six years. " There

are still so many things we don't know. "

 

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