Development of methods for isolating and quantifying mycobactin siderophores in tuberculosis.
Tuberculosis (TB) is the 2nd leading infectious killer in the world, resulting in over 1 million deaths per year. Multidrug resistant TB (MDR-TB) is increasing in prevalence. and our last-line antibiotic, bedaquiline (BDQ), is showing signs of failure. Since BDQ is the last-line treatment that is effective against TB infections when all other treatment regiments fail, it is crucial to maintain the effectiveness of this antibiotic for years to come. A gene in tuberculosis, known as rv0678, is the culprit for drug resistance in different bacterial strains. The rv0678 gene is responsible for the regulation of an efflux pump system in TB cells, and mutations within this gene are exhibiting resistance to antibiotics, such as BDQ. The efflux pump facilitates the export of siderophores, which are proteins responsible for chelating iron. We are interested in measuring siderophore quantities between mutated strains and non-mutated strains of TB to investigate different drivers of BDQ resistance. However, siderophore separation through chloroform extraction is uncommon and a flawed process. The primary objective of this project is to optimize a procedure for isolating and quantifying these siderophores. We hope with this, it will drive our research to obtain a greater understanding of how BDQ resistance is generated in Mycobacterium tuberculosis.
