RNA Pol II inhibitors

RNA Pol II inhibitors from ”nice bacteria”

Bacterial inhibitors of RNA polymerase II

We have identified certain nonvirulent bacteria that control the quality and quantity of host gene expression. With information on the molecules that are responsible for these effects, we can now identify novel molecular concepts to therapeutically enhance beneficial gene expression in the host. We believe this to be a new mechanism that shifts the balance in favor of commensals or symbionts and away from disease.

The new bacterial molecules can be purified and used to suppress inflammation and unwanted gene expression in animal models. This is a promising finding, suggesting that molecules from nice bacteria may be useful drug candidates, in infectious and inflammatory disorders.

Nice bugs inhibit RNA Pol II phosphorylation

Molecular mechanism of Pol II inhibition

We have identified the bacterial genes that inhibit Pol II in human cells and in an animal model

An anti-inflammatory drug

The bacterial molecules can be used as general inhibitors of unwanted inflammatory diseases

Useful bacterium in your bladder, a new friend for life?

The normal flora provides a barrier against attacks from pathogenic bacteria and prevent disease. In addition, certain ”nice bacteria”  also actively reduce the cellular machinery and the symptoms associated with a strong immune response.

In the urinary tract, commensal bacteria cause a condition called asymptomatic bacteriuria (ABU) characterized by a high number of bacteria in the urine but without symptoms. Bacterial carriage prevents the recurrence of infection as the bacteria turn off the inflammatory response by lowering the expression of genes in the host cells.

Our results suggest that bacterial flora can promote their own survival by broadly manipulating the cellular gene expression machinery.  The  bacteria acheive this by suppressing RNA polymerase II activity in inoculated patients and in various human cells after infection. In the cells, the genetic program, carried by the DNA, is read and transcribed into message RNA, which is later, translated into proteins. The first step of gene expression, called transcription, is done by the RNA polymerase II enzyme.A majority of bacteria isolated from individuals with asymptomatic bacteriuria are also able to suppress the RNA polymerase II in the cells.

This mechanism of symbiosis can benefit the bacteria and the host: the bacteria that who be likely to be killed by an immune response; the host that would suffer from the consequences of an immune response like symptoms and sequels.

It is also exiting that the bacterial molecules can be used therapeutically.