There are over 2 million cases of bacterial resistant infections per year in the United States resulting in 23,000 deaths. Most antibiotics, like penicillin, function by targeting elements of bacteria that are not present in higher organisms, such as the cross-linking of the peptidoglycan cell wall. Many antibiotics have been overprescribed and lost their effectiveness, therefore new targets need to be identified that can inhibit or prevent the spread of infection. Our lab has identified the transcription factor Sigma-28 (σ28) as a novel therapeutic target. Sigma-28’s primary role is to initiate transcription of proteins that make up the flagella tail in bacteria. Our working hypothesize is compounds that inhibit Sigma-28 will inhibit flagella formation. Over 100,000 potential inhibitors were computationally screened and 420 were identified as potential candidate inhibitors. After screening these compounds using a high throughput cell-based reporter assay, we have identified 72 of the most effective inhibitors. We are currently using a modified disk-diffusion assay to further screen the effectiveness of these compounds as inhibitors. We are also using a dose response assay to determine an ID50 for the inhibitors. Our preliminary results suggest that Sigma-28 has the potential to be a novel new therapeutic target.

Screening potential inhibitors of the Sigma-28 transcription factor

2019 Spring National Meeting

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