"Understanding how phosphoarginine influences protease function will help us develop drugs that interfere with protease activity, and ultimately help us treat drug-resistant TB infections,” Schmitz said.

Schmitz’s research is now exploring what triggers the creation of these protein modifications.

“We don't know which stresses specifically activate the pathway,” Schmitz said. “We know that these modifications exist, and we have pretty good evidence that their levels are modulated in concert with stress, but the upstream part that connects stress to the actual modification has not yet been mapped.”

The team is also examining the “downstream” aspects of the pathway, such as how changing phosphoarginine levels alters the cell’s behavior, and how this helps the bacteria survive stress.

“It's like a puzzle, and the pieces that we have right now are in the very middle of it,” Schmitz said. “All of the surrounding stuff is uncharted territory.”  

Public health impacts

The work could have enormous implications for public health around the globe, especially in countries where TB is a serious issue. Though the disease is controlled in wealthier nations, nearly half of the people with TB live in only eight countries: Bangladesh, China, India, Indonesia, Nigeria, Pakistan, Philippines and South Africa.

“There might not be a lot of cases in the U.S., but where I'm from, for example — Nepal — there are still a lot of tuberculosis cases. People are really struggling,” Kandel said. 

“It’s particularly rewarding to study a disease that disproportionately impacts regions with limited research resources,” Schmitz said. 

Despite the potential impact, the team is staying focused on the science of what Schmitz calls “new biology” as this area has been previously unexplored.  

“It’s hard to think about the magnitude of tuberculosis every day,” Anderson said. “But to be able to work on novel pathways that could actually make a difference is really cool.”