“Teeth are an excellent source of DNA,” says Kirsten Bos, an anthropologist at the Max Planck Institute for the Science of Human History who worked on the new study. Dental pulp—the soft, living tissue inside teeth—is full of blood vessels and thus any pathogens that once circulated in the blood. And hard enamel on the outside protects the DNA of those pathogens for centuries.

Bos and her team have previously identified plague bacteria in the teeth of Black Death victims, but the cocolitzli samples presented a different challenge. Scientists already suspected that the Black Death was caused by the bacteria Yersinia pestis, but no one is as certain about the exact cause of cocolitzli. So Bos’s team repurposed a method called metagenomics that sequences all of the DNA in a sample, generating a long list of all bacteria present in the teeth. One researcher went through the list by hand, and a specific strain of Salmonella enterica popped up repeatedly. Dental pulp samples from five people who died before European contact but buried in the same site contained no significant amounts of S. enterica.

Paratyphoid fever spreads through food or water contaminated with the feces of a sick person. Today, it usually breaks out when people live in poor, crowded conditions. It’s possible that the Spanish, in addition to bringing the bacteria, relocated people and instituted agricultural practices that exacerbated its spread. The symptoms, broadly, match up, though historical accounts—written before the advent of germ theory—are evocative if not clinically specific. For example, the Franciscan friar Fray Juan de Torquemada wrote in 1576:

The fevers were contagious, burning, and continuous, all of them pestilential, in most part lethal. The tongue was dry and black. Enormous thirst. Urine of the colors sea-green, vegetal-green, and black, sometimes passing from the greenish color to the pale. Pulse was frequent, fast, small, and weak—sometimes even null. The eyes and the whole body were yellow. This stage was followed by delirium and seizures. Then, hard and painful nodules appeared behind one or both ears along with heartache, chest pain, abdominal pain, tremor, great anxiety, and dysentery.

The study authors acknowledge that S. enterica may have interacted with other circulating pathogens. The method does not rule them out. In particular, the team can only detect DNA, but some viruses carry RNA instead. “If all these people died from RNA viruses, we will never know, at least not with these techniques,” says Nicolas Rascovan, a microbiologist at Aix-Marseille Université, who also studies dental-pulp DNA among people in the Americas.

Acuña-Soto still favors his viral hemorrhagic-fever hypothesis, and he notes that Salmonella has never caused another epidemic as deadly as cocoliztli in recorded history. The strain most similar to the one found in the 16th-century teeth is rare and not well-studied, but it has a 10 to 15 percent mortality rate today. It is also not entirely known whether Salmonella was present in the Americas before contact with the Spanish or how pervasive it was in Europe.