The latest findings, published in the journal Emerging Infectious Diseases, could explain why the plague suddenly breaks out in countries such as Madagascar, where the disease killed 202 people last year.
There have also been outbreaks in the US, with 16 cases including four deaths in 2015.
David Markman, from Colorado State University, who led the study, said that plague is endemic in many parts of the world and its origins are still not really understood.
Mr Markman said: “The interesting and troubling part of plague, and part of the reason why there are so many unanswered questions, is that it is present in many different environments – from the jungle to the desert and everywhere in between.
“It’s difficult to find one mechanism that unites all these different locations which explains when, where and why plague breaks out when it does.”
The Black Death is a highly contagious disease that has killed millions of people over the past 1,400 years.
The Plague is still a real threat to the world, with it occurring in as many as 36 countries.
During the middle ages, the Black Death swept through Europe killing an estimated 75 to 200 million people.
The researchers found amoebae, bugs that live in soil and water.
These are known breeding grounds for disease, as possible offenders that are protecting the plague bacteria.
The researchers took soil samples to test their theory.
These were taken from the burrows of the prairie dogs of northeastern Colorado, which are known hosts of the plague.
The team isolated five species of amoebae and then integrated them with plague bacteria to see how they would react.
By using a genetically altered strain of plague that glows green, the scientists observed the amoebae ingesting the plague.
They then saw that the plagues pathogens were alive and replicating in the amoebae.
Mr Markman warned that his research had worrying implications for bioterrorism.
He said: “Some nefarious agent or actor could easily infect an amoeba and the amoeba could be spread into the water supply or sprayed over a crop field.
“There are hundreds of other human and animal pathogens that can survive and multiply inside amoeba but throughout all humanity, plague is the most deadly pathogen we have seen,”
Tedros Adhanom Ghebreyesus, director general of the World Health Organisation, called on the international community to do more to help understand why plague outbreaks occur.
He said: “Who will continue to support plague preparedness, control and response, and we call on our international development partners to help us end human outbreaks.
“This will include a better understanding of the wider factors that allow plague to spread, and strengthening national capacities to manage similar emergencies in the future.”