Grant: Project Grant

Pseudomonas aeruginosa is a bacterium that poses a serious threat to people with cystic fibrosis and other immune-compromised conditions. To survive and thrive, this organism uses specialized machinery to deliver toxic proteins into surrounding cells. These machines, known as type VI secretion systems (T6SSs), act like molecular syringes that inject toxins to eliminate competitors or damage host tissues. While two of the known T6SSs in P. aeruginosa are well understood and primarily target other bacteria, the third system, known as the H3-T6SS, has remained a mystery. Recent work from our lab has revealed that the H3-T6SS likely functions very differently. We have discovered that this system exports a unique set of toxic proteins that do not harm bacteria but are highly damaging in other biological systems. Some of these toxins resemble known virulence factors from other dangerous pathogens and appear to require host-specific molecules to become active. We have also identified the machinery responsible for loading and exporting these effectors from the bacterium, as well as a rare clinical strain of P. aeruginosa that turns this system on more readily, giving us an unprecedented opportunity to study how it is regulated. This project will uncover how these toxins function, how they are exported by the bacterium, and what triggers their release. By investigating this poorly understood secretion system, we aim to shed light on how bacteria harm their hosts during infection and lay the groundwork for new strategies to disrupt these processes in infectious disease.