Many bugs that make us sick -- bacteria, viruses, fungi and parasites -- hide out in our cells in protective little bubbles called pathogen-containing vacuoles (PVs). To clear an infection, the immune system must recognize and destroy these vacuoles while leaving the rest of the living cell intact.

Because PVs provide an intracellular niche permissive for microbial growth, their destruction is critical for host defense.

When pathogens first enter a host cell, they take part of the plasma membrane with them, wrapping it around themselves like a cloak to mask their true identity. Eventually, a healthy immune system discovers the invasion and puts special molecules called guanylate binding proteins (GBPs) on high alert. These proteins specifically bind to the membranes of the pathogen-containing vacuoles and eliminate the infiltrators.

Although it has been shown that GBPs translocate to and eliminate PVs, the mechanisms by which GBPs specifically bind to PVs were unknown.

Researchers in the journal PNAS describe an immune pathway that results in the decoration of PVs with a small protein called ubiquitin. Ubiquitin-decorated PVs are subsequently recognized by GBPs, resulting in the elimination of PVs and their microbial inhabitants.

The researchers also showed that highly virulent strains of Chlamydia and Toxoplasma contain special factors that block the addition of these ubiquitin tags. Because their vacuoles don't get ubiquitinated, the GBPs fail to recognize them as the enemy.

http://today.duke.edu/2015/09/kissofdeath