We employ structural biology and biophysics to reveal the biological and molecular function of key bacterial protein toxins delivered by the Type VI Secretion System (T6SS) of the human pathogen Pseudomonas aeruginosa. The T6SS delivers toxins into target cells. These toxins are essential to allow P. aeruginosa to outcompete other bacteria, providing a fitness advantage and facilitating infections. P. aeruginosa is a bacterial pathogen that causes one in ten of all hospital-acquired infections. Most commonly, it infects the airway, burns, wounds, urinary tract, and blood. It is one of the primary causes of pneumonia in immunocompromised people and individuals with lung diseases. It causes approximately 80% of lung infections in people with Cystic Fibrosis (CF). Unfortunately, due to its high level of intrinsic and acquired resistance against most common antibiotics, it has become increasingly challenging to treat P. aeruginosa infections.

We expect that our research will significantly contribute to understanding how P. aeruginosa utilise the T6SS to colonise and persist in a setup of polymicrobial infections. Remarkably, this knowledge could help to develop innovative strategies to fight antimicrobial resistance. Bacterial infections remain a leading cause of death worldwide. A critical global problem is the development of antibiotic resistance, which is considered by the World Health Organization (WHO) as one of the three most significant threats to human health for the next decades. The WHO estimates that by 2050, antimicrobial resistance could give rise to over 10 million deaths yearly. In 2017, the WHO published a list of human pathogens requiring urgently developing new antibacterial treatments. P. aeruginosa is ranked within the top three pathogens in “critical” need of antibiotic development.