Mentor: Monica Chander
The Streptomyces coelicolor bacterium produces several compounds that contain antibiotic properties. The goal of this research is to determine how S. coelicolor avoids self-destruction by a specific redox-active antibiotic, actinorhodin (Act). There is evidence that Act is removed from the cell through a membrane transporter (Act exporter). However, a strain that is mutated for the Act exporter was found to be viable, which suggests that S. coelicolor has another mechanism that allows it to resist Act. An alternative Act-resistance mechanism is hypothesized to be the redox-regulated SoxR transcription factor. This is based on previous observations that SoxR-regulated genes include membrane transporters and enzymes that resemble antibiotic-metabolizing proteins. Not only that, but SoxR-regulated genes are expressed only when the bacterium synthesizes Act, with the soxR null mutant strain overproducing Act. This implies that SoxR normally regula tes the production of this antibiotic. The soxR mutant strain is also viable, which is why we propose that these two mechanisms both contribute to Act resistance and compensate for each other if one malfunctions. One prediction is that the mutant strain with both deficiencies will display reduced fitness in comparison to the wild type strain and the strains that are mutated for each of the mechanisms. We will test this hypothesis thissummer by constructing the necessary mutant strains and analyzing them.