Bacteria have to be able to defend themselves from other microbes and can do so with antibiotics. That’s made the soil-dwelling strains of Streptomyces a source of many antibiotics. To make those antibiotics, the life cycle of the Streptomyces microbe has to be carefully controlled and end in a process called sporulation, in which spores are formed. That enables microbes to enter a dormant state in which they can survive dangerous conditions. Now researchers at the John Innes Centre have discovered a critical protein that ensures that sporulation events are timed correctly.
They found the DNA-binding protein that can put the brakes on the Streptomyces life cycle is called BldC. Reported in mBio, this protein may help scientists ramp up the production of useful antibiotics.
In this work, the researchers showed that when the gene encoding for BldC is gone, sporulation starts too soon. To learn more about how BldC regulates that timing, they turned to Chromatin-Immunoprecipitation-sequencing. That showed exactly where BldC was binding to the Streptomyces chromosome. Then, they assessed which genes were active in the microbe by sequencing its RNA.
"This approach showed that the BldC brake works by keeping important genes required for sporulation switched off at a time when Streptomyces wants to grow non-reproductively," explained the first author of the report Dr. Matt Bush.
"To our surprise, these studies showed that as well as switching some genes off, BldC can also switch other genes on. Because BldC binds at many positions on the chromosome, one possibility is that it also serves to organize the chromosome's structure - it's a nucleoid-associated protein."
The researchers employed a strain of the bacterium called Streptomyces venezuelae, which can sporulate in liquid as well as on agar plates, unlike other versions. That enabled the researchers to get a good look at the processes inside.
"This means we can use time-lapse fluorescence microscopy to make movies of Streptomyces undergoing the entire spore-to-spore life-cycle in real-time. We can put a fluorescent "tag" on a protein in the cell to see where it goes and when. Here we put a tag on the "FtsZ" protein that is required for the cell division event that produces spores." said Bush.