Biophysical Society Thematic Meeting - November 16-20, 2015

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts

Combining Structural Genomics and Drug Discovery to Develop New TB Drugs James Sacchettini . Texas A&M University, College Station, USA. Although there are multiple effective drugs available for treating tuberculosis (TB), current strategies are greatly complicated by the long chemotherapy treatment that lasts several months. Widespread patient non-compliance has contributed to the emergence of multidrug-resistant (MDR) and extensively drug resistant (XDR) TB strains. There is a clear need for novel fast acting drugs that are capable of eliminating an infection in just a few weeks. Our lab, in conjunction with the TB Drug Accelerator and the Structural Guided Drug Discovery Consortium, has focused on the identification of new drug targets. Our long-term goal is to identify fast acting lead compounds that would simplify chemotherapy regimens for treating resistant infections. A significant step forward has been the use of whole cell actives for high- throughput screens and subsequent target identification methods for drug development. We now have two compounds in lead-optimization for TB. Light Forge: A Microfluidic High Throughput Platform for Rapid and Affordable Detection of Drug Resistant Strains of Tuberculosis Ian Mbano , Tawanda Mandizvo, Frederick Balagadde. K-RITH, Durban, Alabama, South Africa. Light Forge is a new scalable microfluidic platform developed at K-RITH for the genomic interrogation of Mycobacterium tuberculosis strains using Real-Time PCR and High Resolution Melt Analysis (HRMA) on a chip. We have used this system to identify clinical Tuberculosis strains that are resistant to Rifampicin (a frontline drug in treatment of tuberculosis) relative to a susceptible strain H37Rv based on mutations on the RpoB gene. Lightforge has the potential to contribute towards a low-cost solution to diagnosis of multidrug resistant tuberculosis- a critical global healthcare challenge. Lightforge has detected mutations linked to rifampicin resistance including single nucleotide polymorphisms (SNPs) in a manner consistent with commercial systems. In preparation for diagnosis of clinical isolates, the Lightforge approach is now being expanded to include detection of resistance to other TB drugs including fluoroquinolones and isoniazid based on mutations in the GyrA, KatG and Mab-inhA.

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