Interfering with plasmid inheritance

Source: University of Sydney

The development of antibiotic resistant strains of bacteria that are problematic and expensive to treat is a major healthcare problem around the world.

The selective pressure of antibiotic usage inevitably results in the emergence and proliferation of resistant bacteria.

Strains commonly become resistant by acquiring a pre-existing resistance gene from other bacteria.

Resistance genes are often carried on plasmids, which can be transmitted from resistant bacteria to sensitive ones, rapidly making them resistant in the process.

In contrast, once a resistance gene is acquired it is usually lost very slowly, if at all, even when the antibiotic is no longer used, because plasmids are inherited very efficiently.

This persistence of plasmids exacerbates the situation because as the bacteria are subsequently exposed to different types of antibiotics they accumulate resistance genes and become increasingly multiple-resistant, leaving fewer and fewer effective treatments.

Currently, there are few options to limit the evolution of resistant bacteria, other than to minimise the unnecessary use of antibiotics.

A research team, which includes Professor Ron Skurray and Dr Neville Firth from the School of Biological Sciences at the University of Sydney and Dr Maria Schumacher from the University of Texas MD Anderson Cancer Centre, is working on new ways to combat resistance.

They have used a plasmid from the drug resistant bacterial pathogen Staphylococcus aureus as a model system to study a process fundamental to all living things, the movement of DNA in dividing cells to achieve faithful inheritance of genetic information, called partitioning.

The research has provided a detailed picture of the protein-DNA complex at the heart of the process, which can be targeted to disrupt the partitioning of plasmids and consequently the resistance genes carried by them.

"It's an increasingly urgent problem and these results are a step towards doing something about it," Firth said.

"The challenge now is to use the findings to develop specific agents and strategies to interfere with plasmid inheritance so we can turn the tables on the resistance problem by promoting the loss of resistance genes.

"If this can be done, it would be possible to re-establish the effectiveness of some compromised antibiotics, as well as extend the useful working life of current and future treatments," he said.

The paper, Segrosome structure revealed by a complex of ParR with centromere DNA, appears in the current issue of Nature (letters).