The path by which pathogenic bacteria inject toxic molecules into host cells is visualized for the first time in a study published online this week in Nature Structural & Molecular Biology.
Type-3 secretion systems (T3SSs) are highly-conserved protein machineries that inject bacterial toxic molecules, known as virulence factors, directly into host cells, thereby modulating the host cell’s functions. Central to T3SSs is the injectisome, a syringe-like needle complex anchored in the bacterium that is believed to provide a path for the virulence factors to enter targeted cells.
Thomas Marlovits and colleagues used structural biology and imaging techniques to show how Salmonella T3SS transfers virulence factors into host cells. They were able to create a three-dimensional model of the injectisome with an engineered substrate molecule and then visualize the entire T3SS apparatus in the process of secreting substrate. Marlovits and colleagues found substrate molecules passing through the central “bore” of the injectisome complex, indicating that virulence factors must first unfold in order to be passed through to the host cell.
As T3SSs are essential to the virulence of a variety of pathogenic bacteria, blocking the pathway to host-cell entry via T3SSs may be a promising therapeutic approach to battle bacterial infections.