ABSTRACT:
Maintaining an optimal level of chromosomal supercoiling is critical for the progression of DNA replication and transcription. Moreover, changes in global supercoiling affect the expression of a large number of genes and play a fundamental role in adapting to stress. Topoisomerase I (TopA) and gyrase are key players in the regulation of bacterial chromosomal topology through their respective abilities to relax and compact DNA. Soil bacteria such as
Streptomyces
species, which grow as branched, multigenomic hyphae, are subject to environmental stresses that are associated with changes in chromosomal topology. The topological fluctuations modulate the transcriptional activity of a large number of genes and in
Streptomyces
are related to the production of antibiotics. To better understand the regulation of topological homeostasis in
Streptomyces coelicolor
, we investigated the interplay between the activities of the topoisomerase-encoding genes
topA
and
gyrBA
. We show that the expression of both genes is supercoiling sensitive. Remarkably, increased chromosomal supercoiling induces the
topA
promoter but only slightly influences
gyrBA
transcription, while DNA relaxation affects the
topA
promoter only marginally but strongly activates the
gyrBA
operon. Moreover, we showed that exposure to elevated temperatures induces rapid relaxation, which results in changes in the levels of both topoisomerases. We therefore propose a unique mechanism of
S. coelicolor
chromosomal topology maintenance based on the supercoiling-dependent stimulation, rather than repression, of the transcription of both topoisomerase genes. These findings provide important insight into the maintenance of topological homeostasis in an industrially important antibiotic producer.
IMPORTANCE
We describe the unique regulation of genes encoding two topoisomerases, topoisomerase I (TopA) and gyrase, in a model
Streptomyces
species. Our studies demonstrate the coordination of topoisomerase gene regulation, which is crucial for maintenance of topological homeostasis.
Streptomyces
species are producers of a plethora of biologically active secondary metabolites, including antibiotics, antitumor agents, and immunosuppressants. The significant regulatory factor controlling the secondary metabolism is the global chromosomal topology. Thus, the investigation of chromosomal topology homeostasis in
Streptomyces
strains is crucial for their use in industrial applications as producers of secondary metabolites.