Bistable Gene Expression in Pseudomonas aeruginosa

Pseudomonas aeruginosa, the most important antibiotic-resistant hospital acquired infection disease, makes use of the bistable expression process to increase its survival and become more pathogenic. Because of this phenomenon, genetically identical bacterial cells may be made to exist in two different states of adapting to a foreign environment, thereby permitting the bacterial population to respond within any given time frame to an unfavourable environment, as in the case of a hospital.

Key Findings:

• The study centered on glpD gene that plays a role in glycerol metabolism and is associated with the infection causing characteristics of the bacterium.
• In contrast to most highly-expressed genes, glpD is highly variable with some cells expressing it at high levels (on state) or at low or undetectable levels (off state).
• Network This bistability is epigenetically inherited , such that daughters cells carry the expression state of their parent for several generations and then may switch.

How It was Discovered

Scientists incorporated fusion of regulatory DNA of glpD and a gene of green fluorescent protein (GFP). This enabled them to visualize how a gene worked in single cells. It was only a fraction of the cells which appeared green, making a confirmation of the bistable states (on and off).

Effect on Infection:

• Bacteria that lack the glpD gene were weaker in inducing infections in animal testing models.
• Exposure to host immune cells elevated the expression of glpD indicating that this virulence phenotype can be induced by the environment within the host.

Why It Matters

Bistability leads to the fact that a small population of bacteria will always have a subpopulation of highly infectious, in the state-one cells primed to cause an infection. This pre-adaptation contributes to the increase in antibiotic and immune-resistance of P. aeruginosa. Exploiting the regulatory circuits that drive this bistable state has the potential to translate into new approaches that can be used to fight this virulent pathogen.