With the increasing threat of antibiotic resistance, we must revisit previously investigated bacterial species to activate the cryptic biosynthetic gene clusters not expressed in vitro to discover novel natural product antibiotics.
For example, filamentous Actinobacteria Streptomyces spp. produce specialised metabolites, including 50% of all known antibiotics. However, only 10% of its specialised metabolites are expressed under laboratory conditions. This project works towards switching these cryptic BGCs on to unlock Streptomyces full potential for further novel antimicrobial discovery.
Specifically, Kelly-Rose investigates a signal transduction pathway named the MtrAB pathway using model organism Streptomyces venezuela. This pathway controls antibiotic production via transcriptional regulator MtrA, which is phosphorylated and dephosphorylated by sensor kinase, MtrB.
MtrA is in all Streptomyces species, therefore understanding its regulatory pathway in S. Venezuela could be a large step toward unlocking cryptic BGCs in all Streptomyces species and discovering novel antimicrobials.