Piperacillin triggers virulence factor biosynthesis via the oxidative stress response in <i>Burkholderia thailandensis</i>
Anran Li, Bethany K. Okada, Paul C. Rosen, Mohammad R. Seyedsayamdost
Abstract
Significance Low-dose antibiotics can activate the expression of otherwise silent biosynthetic loci, but the mechanisms underlying this phenomenon are poorly understood. Our results reveal several classes of molecules that globally induce secondary metabolite biogenesis in the model bacterium Burkholderia thailandensis . We illuminate the mechanism of induction of one of these elicitors, the β-lactam piperacillin, and uncover oxidative stress as a new input that initiates synthesis of the virulence factor malleicyprol. The finding that malleicyprol is a component of the oxidative stress response indicates that B. thailandensis has evolved to trigger virulence when faced with reactive oxygen species. Understanding the links between small-molecule elicitors and otherwise silent biosynthetic programs promises to unlock the structures and regulation of so-far “hidden” natural products.