Identification and characterization of novel antimicrobial resistance and susceptibility markers in Burkholderia pseudomallei.
Abstract
Burkholderia pseudomallei, a potential bioterror agent and causative agent of melioidosis, is naturally resistant to many clinically important antimicrobials and very few drugs are effective against it. There are growing concerns that resistance will continue to arise, through mutation or through acquisition of resistance genes from phylogenetically related near neighbor species or other soil bacteria. Recent studies suggest a greater number of B. pseudomallei strains are susceptible to a wider range of drugs than previously thought. However, the extent of resistance/susceptibility in this pathogen has never been assessed using large diverse strain panels. A better understanding of novel resistance/susceptibility mechanisms in B. pseudomallei would inform improved diagnostics that could be used to rapidly screen clinical specimens and facilitate the appropriate choice of targeted therapeutics. Using a high throughput realtime PCR antibiogram method, we will screen 1,000 sequenced B. pseudomallei and near neighbor isolates for susceptibility to up to 22 clinically relevant antimicrobials, including newly available compounds. Genomes and transcriptomes of isolates identified with expanded and/or novel drug resistance/susceptibility profiles will be explored for potential resistance/susceptibility mechanisms using Genome Wide Association Studies, comparisons between closely related strains that are resistant and susceptible, and RNAseq. This work will lead to a comprehensive understanding of drug resistance and susceptibility mechanisms across a large and diverse collection of B. pseudomallei and near neighbors. Identified mechanisms will be developed into robust and novel tools for rapid drug susceptibility testing, leading to more effective diagnosis and treatment for warfighters and civilians
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 23, 2018
- Source ID
- HDTRA11710051
Entities
People
- Paul Keim
Organizations
- Defense Threat Reduction Agency
- Northern Arizona University