Regulation of antibiotic resistance and virulence by two-component response regulators in Pseudomonas aeruginosa

The bacterium Pseudomonas aeruginosa is a major cause of hospital-acquired infections and chronic cystic fibrosis lung infections. This pathogen is difficult to treat because it has the ability to sense and appropriately respond to changing environmental conditions. For example, it can sense and respond to the presence of antibiotics by becoming resistant, making the eradication of established infections extremely difficult. P. aeruginosa infections in cystic fibrosis patients are almost always deadly. An underlying mechanism for antibiotic resistance involves two-component regulatory systems – containing a sensor kinase and a response regulator – that enable bacteria to sense and respond to environmental signals. Two of these regulatory systems within P. aeruginosa have previously been shown to be involved in antibiotic resistance. Jamie Gooderham is determining whether other closely-related P. aeruginosa two-component regulatory systems are also involved in virulence and antibiotic resistance. To do so, he is generating bacteria defective in these systems and studying their virulence, gene expression, and responsiveness to antibiotics. These studies will increase understanding of how this pathogen adapts to environmental signals to develop antibiotic resistance. Ultimately, this will lead to more effective P. aeruginosa therapies, improving treatment outcomes for infected patients.