Does stripping the cell wall promote survival of Burkholderia in an infected host?

Burkholderia pseudomallei is the causative agent of Melioidosis, a disease predominantly linked to South East Asia and Northern Australia. Currently there are no established treatments or vaccines for Melioidosis. Surviving extreme environmental conditions and causing latent infections which can become reactivated make this pathogen very hard to eradicate, leading to high rates of recurrent infection. B. pseudomallei is of importance for both human health and biodefense due to these features. Understanding the survival mechanisms in vivo will potentially give insights into why Burkholderia are so resistant to treatments.
Published research indicates that starvation conditions at 4C leads to the generation of B. pseudomallei cells which cannot grow in standard media and show a conversion from rods to a rounded coccoid morphology. This can also be seen in other bacteria such as Bacillus subtilis and hypothesized to be the formation of so-called L-forms. These cell wall deficient forms avoid the bactericidal activity from an array of antibiotics which target cell wall related molecules. Increasing evidence suggests L-forms are generated in humans and could be reason for failed treatment and recurrent infections. A recent paper shows Eschericia coli L-forms were responsible for recurrent urinary tract infections.
This project will be aimed to produce a protocol for in vitro L-form formation of Burkholderia species and the detection of L-forms in infected macrophages. The molecular mechanisms which are employed to drive the switching between L-form and actively growing states will also be explored. The results of this project will give a better insight into this special bacterial form which has potential to be the cause of many other treatment failures.