1 research outputs found
Global Awakening of Cryptic Biosynthetic Gene Clusters in <i>Burkholderia thailandensis</i>
Many bacteria encode
biosynthetic proteins that produce a vast
array of natural products. These compounds are often synthesized during
host invasion as they function as virulence factors. In addition,
such secondary metabolites have yielded numerous molecular scaffolds
with pharmaceutical and clinical importance. The gene clusters that
encode proteins responsible for synthesis of these compounds are typically
silenced or “cryptic” under laboratory growth conditions,
hampering discovery of novel lead compounds. We report here that MftR
is a global repressor of secondary metabolite synthesis in <i>Burkholderia thailandensis</i> and that urate functions as a
physiologically relevant inducer of gene expression. Biosynthetic
gene clusters under MftR control include those associated with production
of the antimicrobial bactobolins, the iron siderophore malleobactin,
and the virulence factor malleilactone. MftR also controls additional
genes associated with survival in a host environment, such as genes
encoding components of the type III secretion system (T3SS) and proteins
linked to anaerobic respiration. This observation not only has implications
for understanding activation of gene regulatory networks during host
invasion, but it also paves the way for isolation of novel therapeutic
leads