Sunday, July 24, 2011
Grand Ballroom, 5th fl (Sheraton New Orleans)
The number of single and multidrug-resistant microbial strains has increased rapidly during the last 10 years, however, the number of new antibiotics approved for use has declined. Deciphering the molecular basis of pathogenicity and identifying novel antimicrobial agents has become a high priority in global health care. Next-generation sequencing (NGS) provides new opportunities to identify pathogenicity factors by comparison of clinical isolates at the whole genome level. We have implemented Genedata Selector™ to address the data management and analysis requirements of our NGS-based research process to identify novel antimicrobial agents. The Selector™ system facilitates analysis of pathogenicity profiles across different species and strains isolated from a clinical environment. We have generated a comprehensive set of Listeria genome sequences coupled with phenotype information to provide a reference for comparison with new pathogenic strains. Comparison of clinical isolates with our Listeria genome reference database identified biomarkers that predict pathogenicity. In addition, we have used a systems biology approach to identify new molecules such as small non-coding RNAs which we have demonstrated to be involved in invasion and pathogenicity of Listeria. Furthermore, we integrated diverse experimental results and current knowledge about sRNAs of Listeria within Genedata Selector™ to identify surrogate markers. Finally, we discuss the use of modified peptide nucleic acid (PNA) as a novel tool to inactivate sRNA. Our research suggests PNAs may have applications in rapid and specific detection of pathogenic bacteria and as potential therapeutics.