Antibiotic resistance occurs when bacteria develop the ability to defeat the drugs designed to kill them, causing serious infections to be more difficult to treat. Modern antimicrobials are becoming less effective, while few novel natural products have been discovered in recent years. Streptomyces, a soil-dwelling bacteria, is a prolific producer of antibiotic natural products; more than 75% of natural products come from this genus alone. Bioinformatics analyses have determined that many more natural products reside within Streptomyces’ genomes. Unfortunately, biosynthetic gene clusters are often silent (i.e., not transcribed). This project focuses on exposing Streptomyces to antibiotics they may encounter in the soil to determine if the antibiotics can induce gene expression of natural product biosynthetic enzymes. After Streptomyces bacteria are exposed to oxytetracycline or other tetracycline antibiotics, RNA is isolated and reverse transcribed to DNA, and quantitative PCR is performed. The change in gene expression is analyzed between the control Streptomyces cultures and those treated with oxytetracycline. Future directions include observing natural product response using different chemical elicitors and in new species of Streptomyces. This research has the potential to induce production of novel natural products, which could help serve as leads in the antibiotic pipeline.

Induction of silent biosynthetic gene cluster by tetracycline antibiotics

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