Citation:

Stelma Jr., G N. AND S J. Vesper. ORD/NERL CURRENT VRARS RESEARCH. Presented at Drinking Water Progress Review, Washington, DC, March 2, 2004.

Impact/Purpose:

1. Develop a method, based on microarray analysis, to identify potential waterborne pathogens using the mRNA response in mammalian cells exposed to these pathogens.

2. Develop computational toxicology approach to understanding hemolysins as virulence factors and for predicting virulence of untested microorganisms.

Description:

Virulence is the degree of pathogenicity of a microorganism and virulence factors are the components of an organism that contribute to virulence. Identifying microorganisms using known virulence factors is one method used by microbiologists to distinguish pathogenic isolates from non-pathogens. This does not always work because an a sequential series of these factors is often needed for an organism to be pathogenic and to date most of these factors are still unknown. Virulence factor activity relationships (VFARs) refers to the hypothesized structure-activity relationships among virulence factors possessed by different pathogens. By examining VFARs, we could potentially identify pathogenic strains within a species and possibly currently unrecognized pathogens. There are some limitations to this approach in the immediate future because so many virulence factors are still unknown and we do not know the extent to which the biological world parallels the chemical world with respect to structure-activity relationships. We do know that some virulence factors are genetically similar in species that are not closely related; whereas, others appear to be unique to one genus or species. NERL researchers have developed an approach that could potentially circumvent the need to know all of the virulence factors possessed by a particular genus or species. This approach involves measuring the responses of host cells to known pathogenic strains and compare them to the response of non-pathogens. This is being accomplished by infecting cell cultures and quantitatively measuring the specific messenger RNAs that are produced in each case, using microarrays that include the entire genome of the host species. Although pathogens with different types of virulence mechanisms, may elicit somewhat different messenger RNA signals, it is hoped that these signals will at least allow us to identify broad classes of pathogens. The end result will be a database of RNA response profiles from known pathogenic strains that can be compared to similarly derived profiles from uncharacterized strains

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