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Research

Genomics

Using recent innovations from genomic sciences, ASRI researchers are changing our understanding of medical approaches to treating bacterial infections, such as non-healing wounds. Diabetic ulcers, pressure ulcers and other non-healing wounds present physicians with a difficult challenge. Because these wounds may be infected by a wide array of pathogens, they are often difficult to diagnose. In turn, that delays treatment for the patient.

“Quite often, non-healing wounds are infected by biofilms, a highly organized community of self-regulating microbes that attach themselves to tissue or inanimate surfaces,” explained Garth Ehrlich, PhD, Director of the Center for Genomic Sciences at ASRI. “Biofilm’s mechanism of antibiotic resistance makes it a difficult infection to treat. Furthermore, biofilms are not as easily diagnosed as standard cultures.”

Using cutting-edge DNA-based technology, ASRI genomic scientists are testing a nucleic acid-based detection system that can identify specific strains of bacteria and fungi — as well as infectious agents such as MRSA or the H1N1 virus — without the need for culture.

“Originally, this technology was developed for the military to detect various biological warfare agents,” said Dr. Ehrlich, who serves as Principal Investigator for this study. “It wasn’t long before the scientists discovered that this surveillance technology could also be used to identify virtually any type of infectious agent.”

The system combines three cutting-edge technologies that provide physicians or scientists with broad-based microbial diagnostics. First, this technology employs multiple PCR-based DNA amplifications targeted to highly conserved genes throughout the bacterial and fungal domains. Next, it employs a novel mass spectroscopic analysis termed ESI-TOF-MS that provides exact DNA base compositions for each of the PCR products. Finally, it utilizes a sophisticated mass look-up table and a computational triangulation approach to arrive at a species-level diagnosis based on the presence/absence and weights of all of the amplified DNA targets.

Dr. Ehrlich and his team of genomic researchers are also studying variability of genes within bacterial species. Using the tools of computational biology and metabolomics, ASRI’s researchers are testing the function of thousands of uncharacterized genes. This could ultimately help physicians determine which bacterial strains within a species are likely to cause a particular type of infection.

“We are just beginning to understand why some people with a strep infection develop an earache, while others develop meningitis or sepsis,” said Dr. Ehrlich. “We have learned that different strains of the same species have very different sets of genes. Thus, some strains only induce mild symptoms, while other strains are killers. By gaining insight into which genes are associated with specific clinical outcomes, this helps us determine the mechanisms by which these genes cause disease. Ultimately, this paves the way for new forms of treatment that can be tailored for each patient.”

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