Event Title
Next-Generation Sequencing Analysis of Mycobacteria Resistant to Fluoroquinophenoxazine Compound
Presenter Name
Pamela K. Garcia
Student or Staff
Graduate/Undergraduate
Submission Type
Talk
Start Date
11-11-2017 8:30 AM
End Date
11-11-2017 10:00 AM
Description
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, which has become a serious global health problem. The emergence of different levels of resistance in this organism generates complication in the treatment and the necessity of exploring novel targets and develops new drugs. Sun285 is a fluoroquinophenoxazine compound that has shown promising activity against Mycobacterium tuberculosis; in this study we explore the mechanism of action and mycobacterial resistance mechanisms associated to this drug using Mycobacterium smegmatis as model organism.
Mycobacterium smegmatis resistant mutants were isolated through a stepwise mutation process in order to generate mutations associated with drug resistance. In total 18 resistant mutants were isolated at concentrations between 3.0-18.0 μM (MIC=0.3 μM). Whole genome sequencing of all the isolated was performed through Next Generation Sequencing (MiSeq-Illumina) and further data analysis performed in the Genomics Workbench Software 10 (QIAGEN).
Mutations associated to general drug resistance; essential genes for Mycobacterium tuberculosis and hypothetical genes involved in metabolic processes were found. These mutants and mutation have been analyzed to determine if any of the mutations may be specific for the antibacterial action of the fluoroquinophenoxazine compound.
Keywords: Tuberculosis, Whole Genome Sequencing, Genomics, Mutations and Drug Resistance.
Next-Generation Sequencing Analysis of Mycobacteria Resistant to Fluoroquinophenoxazine Compound
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis, which has become a serious global health problem. The emergence of different levels of resistance in this organism generates complication in the treatment and the necessity of exploring novel targets and develops new drugs. Sun285 is a fluoroquinophenoxazine compound that has shown promising activity against Mycobacterium tuberculosis; in this study we explore the mechanism of action and mycobacterial resistance mechanisms associated to this drug using Mycobacterium smegmatis as model organism.
Mycobacterium smegmatis resistant mutants were isolated through a stepwise mutation process in order to generate mutations associated with drug resistance. In total 18 resistant mutants were isolated at concentrations between 3.0-18.0 μM (MIC=0.3 μM). Whole genome sequencing of all the isolated was performed through Next Generation Sequencing (MiSeq-Illumina) and further data analysis performed in the Genomics Workbench Software 10 (QIAGEN).
Mutations associated to general drug resistance; essential genes for Mycobacterium tuberculosis and hypothetical genes involved in metabolic processes were found. These mutants and mutation have been analyzed to determine if any of the mutations may be specific for the antibacterial action of the fluoroquinophenoxazine compound.
Keywords: Tuberculosis, Whole Genome Sequencing, Genomics, Mutations and Drug Resistance.