A team led by researchers from the Centro Nacional de Biotecnología (CNB-CSIC) has discovered the mechanism by which a large system of proteins allows the survival of Salmonella inside macrophages, a type of immune system cells that phagocytoses and digests pathogens (bacteria, fungi, parasites...) by enclosing them in a specialized compartment called the Salmonella-Containing Vacuole (SCV).

The work has been published in the scientific journal PNAS and highlights the importance of studying large multi-protein systems to understand infectious disease mechanisms at a molecular level.

To establish an infection, the bacterial pathogen Salmonella needs to overcome multiple cellular defense barriers within the host. One of the most important barriers is the phagocytosis by macrophages, which are able to engulf and destroy microorganisms.

Salmonella has developed sophisticated strategies to survive and proliferate inside macrophages. One of these strategies relies on the formation of a specialized vacuole, the Salmonella-Containing Vacuole (SCV). The SCV protects Salmonella from the antimicrobial environment of the macrophage, allowing the bacteria to replicate and eventually cause disease.

The SCV is not a static compartment, but instead is a dynamic structure whose formation and maintenance requires a delicate balance between the activity of bacterial virulence factors and the host immune response.

To understand how Salmonella controls the composition of the SCV and survive within macrophages, researchers studied the SPI-2 Type Three Secretion System (T3SS-2), a complex molecular machinery composed of more than 30 proteins that acts as a delivery system to inject effector proteins directly into the host cell.

Specifically, the work focused on the characterization of the effector SspH1. Researchers solved its atomic structure and performed cell biology assays to elucidate its function inside infected macrophages.

The results, combined with previous data on other effectors, allowed researchers to propose a general mechanism by which an intricate system of effectors work coordinately to remodel the SCV and ultimately favor bacterial survival.

These findings provide important insights into the complex interplay between bacterial virulence factors and the host immune response during intracellular infections. Furthermore, the results are relevant from the therapeutic perspective, because targeting this multi-protein system could be a potential strategy to develop new treatments against Salmonella infections.