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For Laboratory Researchers – Microarray Technology

Unraveling MRSA's Deadly Secret with Microarray Technology

Robert S. Daum, MD, "The Staph aureus doctor," is working to discover why MRSA (methicillin-resistant Staphylococcus aureus) strains have become epidemic among healthy people. MRSA is now the most common infectious disease discharge diagnosis in the United States. To best prevent, contain, treat, and manage MRSA disease, scientists need to understand why new MRSA strains—ones that are circulating in the community, not in hospitals—have become so adept at causing disease.

A crucial tool in understanding this problem is microarray technology. A microarray computer chip is the size of a bottle cap, but can provide an organized display of microscopic spots that together represents the entire genetic content of a MRSA strain. Microarrays can be used to compare genes between different strains of MRSA and evaluate what turns them on (or off). Microarray technology allows the MRSA Research Center Laboratory to understand distinctions between MRSA strains and help answer the puzzling question, "Why do some MRSA germs cause extensive disease and others seem to be almost unable to cause any disease at all?"

CA-MRSA Mircroarray Technology - Research Goals

  • To identify the genetic basis for the increased potential of the new community-associated MRSA (CA-MRSA) strain to cause disease.
  • To identify which genes in the more virulent isolates of CA-MRSA are responsible for causing severe disease.

Background

We know abnormal genes or chromosomes cause many diseases.  Just a single change in the DNA sequence of an individual can dictate whether they are resistant to HIV infection or whether they will be stricken with cystic fibrosis, for example.  A similar idea can be applied to the study of bacterial pathogens.

New Variant of MRSA: Community-Associated MRSA

A new variant of MRSA bacteria, recently discovered, is uncharacteristically striking previously healthy individuals with few known risk factors and is circulating in epidemic proportions in the community.  The most serious cases like severe sepsis, necrotizing pneumonia, and necrotizing fasciitis often result in amputation or death.

Using a technique known as "fingerprinting," we can readily distinguish the traditional healthcare-associated MRSA strain from the new epidemic community-associated strain. We have found that this new strain of MRSA (called "USA300") has a genome pattern (called a "fingerprint") that is distinct from the previously more common strain that mainly affects people with healthcare-associated risk factors.

Research Question

Why are some people afflicted with extremely serious life threatening disease while others are afflicted with less complicated disease, even though they appear to be infected with the same strain of MRSA bacteria (USA300)?

We believe the answer to this question might lie in the distinctions in bacterial genomes between different bacteria isolated from separate patients.  We have seen slight variations in the genome fingerprint between bacteria classified as strain USA300 that were obtained from different patients, suggesting slight genetic differences between separate isolates of the USA300 strain.

We hypothesize that such slight differences in genetic content between different USA300 isolates could explain why some people are afflicted with extremely serious life threatening disease while others are afflicted with less complicated disease.

Microarrays Can Help Us Explore the Answers to these Research Questions

A microarray is a small solid substrate (as small as 2x2") that allows for the characterization of the genetic content of an unknown organism.  This is possible by comparing the unknown organism with a characterized organism.  The microarray itself consists of an organized array of microscopic spots that altogether represents the entire genome of a well-characterized organism of interest.

Each spot on the array represents one gene from the organism's chromosome.  By placing a spot for each gene from the chromosome of a known organism on the microarray and reacting it with specially labeled DNA from an uncharacterized strain, the genes that are similar between the two strains will "light up" on the array and genes that are missing from the test strain will not light up.

Thus, we can compare whether the genome content of the unknown organism is similar, or different, and whether there are genes missing from one strain compared with another.

This same technology can be used to compare the expression of genes between two strains of interest.

Summary

In summary, microarrays can be used to:

  • Compare genes that are silent with genes that are expressed.
  • Determine whether genes are expressed to a greater degree in one strain compared with another strain.