Imagine battle armor that is so effective it continually transforms itself—adapting to protect its wearer from fast-changing assaults. In the microbial realm, the wearer is a pathogen that uses its responsive armor—consisting of the varying protein coats on its surface—to fend off the host’s immune-system defenses.

“These pathogens keep changing their coats, fooling whatever the immune system sends after them,” says HHMI international research scholar Hugo D. Luján, who studies surface-protein regulation in the intestinal parasite Giardia lamblia at his laboratory at the Catholic University of Cordoba in Argentina. Whether the pathogen defenses are compared to beasts with ever-changing scales or bandits with different disguises, the surface-protein variation poses major challenges to medicine.

Now that genomic analyses have identified the genes that express surface proteins, scientists are focusing on how pathogens detect attacks from the human immune system and quickly change their coats. That process, called antigenic variation, allows the microbe to evade the host’s immune response and extend the length of infection. And by making it difficult for the host to identify the microbial invader, it opens the door to reinfection and increases the odds that the disease will be transmitted to more human hosts.

Illustration by Mattias Adolfsson