Bistable Gene Expression in Pseudomonas Aeruginosa
Recent research has uncovered that the bacterium Pseudomonas aeruginosa exhibits bistable gene expression, a phenomenon where identical cells show different levels of gene activity. This discovery sheds light on how this deadly pathogen adapts and survives in hostile environments such as hospitals. The study focuses on the glpD gene, which shows variable expression linked to the bacterium’s ability to cause infections. Understanding this mechanism is crucial because P. aeruginosa is a major cause of hospital-acquired infections and is often resistant to antibiotics.
Bistability in Microorganisms
Bistability refers to the existence of two distinct expression states of the same gene within genetically identical cells. This variation can be inherited by daughter cells, a process called epigenetic inheritance. It allows bacteria to diversify their behaviour and adapt to changing environments. In Pseudomonas aeruginosa, bistability may help the pathogen survive immune responses and antibiotic treatments.
The glpD Gene and Its Role
The glpD gene in P. aeruginosa encodes an enzyme involved in glycerol metabolism. Researchers found that glpD expression varies widely among individual bacterial cells. Some cells express it at high levels while others at low or none. This variation is unusual because glpD is a high expression gene (HEG), which normally shows less variability. The dual expression states suggest that glpD can behave as both a high and low expression gene depending on the cell.
Tracking Gene Expression with Fluorescent Proteins
Scientists fused the regulatory DNA of glpD with a green fluorescent protein (GFP) gene. Cells expressing glpD also produced GFP, glowing green under specific light. This allowed real-time observation of gene activity at the single-cell level. Only a small fraction of cells glowed, and this ‘on’ state could persist for several generations. However, daughter cells from one ‘on’ cell sometimes switched ‘off’, indicating dynamic bistability.
Impact on Pathogenicity
Experiments using larvae of the greater wax moth showed that bacteria lacking glpD had a reduced ability to cause infection. This confirmed the gene’s role in pathogenicity. Additionally, P. aeruginosa cells interacting with mouse immune cells showed increased glpD expression. This suggests that the host environment influences gene activity, enhancing the bacterium’s infectious potential.
Implications
The presence of bistability means that even small bacterial populations can initiate infections, as some cells will express virulence genes at high levels. This variability might contribute to the pathogen’s resilience and resistance to treatments. Understanding bistable gene expression could help develop new strategies to combat P. aeruginosa infections by targeting gene regulation mechanisms.
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