Toxin-antitoxin systems negatively control plasmid replication

According to Thomas Wood, Biotechnology Endowed Chair and Professor of Chemical Engineering at the Penn State College of Engineering., toxin-antitoxin (TA) structures are currently known to adversely regulate the replication of plasmids.

Plasmids are extra-chromosomal bits of DNA that enable bacteria to resist antibiotics, rendering the antibiotics ineffective in preventing bacterial infections.

According to Wood, the presence or absence of plasmids affects the resistance of a bacterium to antibiotics and its ability to induce infection—crucial points relevant to combat bacterial infections.

Each year, there are at least 700,000 deaths worldwide because of bacterial infections, a growing number that is projected to increase to 10 million by 2050. And of course, the effectiveness of antibiotics is critical to healing from any type of bacterial infection.”

Thomas Wood, Biotechnology Endowed Chair and Professor of Chemical Engineering, Penn State College of Engineering

In a new issue of the Proceedings of the National Academy of Sciences, Wood and his collaborators have described a feature of a certain TA scheme, called PrpT/PrpA. The PrpA antitoxin inhibits plasmids from replicating too few or too many copies, which subsequently causes the bacteria to resist antibiotics at the cellular level.

Though they are not alive, plasmids are selfish in their behaviors. The plasmid seeks to stay in bacterial cells, so it very carefully controls the number of copies it creates; not too many copies that it becomes a burden to the bacterial cell, and not too few that some bacteria cells do not have a copy.”

Thomas Wood, Biotechnology Endowed Chair and Professor of Chemical Engineering, Penn State College of Engineering

For many years, it has been known that plasmids are responsible for antibiotic resistance, but this is the first time where a TA system has been associated with the replication of plasmids.

The antitoxin acts as an unexpected player in the negative control of plasmid replication.”

Thomas Wood, Biotechnology Endowed Chair and Professor of Chemical Engineering, Penn State College of Engineering

Although scores of TA systems are found in each bacterial type, as in the case of extensively researched E. coli, the research team is now only discovering what these microorganisms actually do, added Wood.

To support the organization and classification, Wood and his collaborators have recently released an article in the Trends in Microbiology journal to help organize all the seven ways used by antitoxins to interact with toxins. During his career, Wood has identified and named the first type in Category V as well as the first two types in Category VII, which also includes the HEPN/MNT system.