A College of Medicine researcher is developing a new antibiotic related to penicillin to treat tuberculosis (TB) and related lung infections.
Kyle Rohde, an infectious disease expert, recently received a $3.4 million, five-year grant from the National Institutes of Health to create new antibiotics that target mycobacterial infections caused by pathogens such as Mycobacterium tuberculosis and Mycobacterium abscessus.
TB infected 11 million people in 2021, ranking it 13th as the leading cause of death worldwide. While TB numbers started to decline during COVID-19, they are rising again. The infection spreads through airborne droplets released when an infected person coughs or sneezes. Symptoms include coughing up blood, difficulty breathing, fever and chills. If left untreated, TB can be fatal.
“Thankfully, only 1 in 10 people who get infected develop symptoms in the short term. But infected people who don’t get sick right away can still develop so-called latent infections and can be carriers for years,” says Rohde. “If the infection is not detected and treated early on, the bacteria can enter the patient’s bloodstream and spread to various parts of the body such as bones, brain and liver.”
Although rare in the U.S., TB infections are prevalent globally with high numbers found in places like India, China, sub-Saharan Africa, Russia and Brazil and spreads easily in crowded populations.
The current standard treatment for TB involves a combination of drugs taken over four to six months or much longer for drug-resistant strains. Treatments of M. abscessus infections are even longer, less effective, and require IV antibiotics. However, due to the side-effects and duration of these regimens, many patients fail to complete their treatment.
Rohde’s research aims to develop new treatments that shorten treatment times, eradicate drug-resistant strains and minimize side effects.
Penicillin, the prototype of one of the oldest and most used class of antibiotics known as beta-lactams, is not effective against mycobacteria. However, Rohde says, “We’re starting to understand why the old penicillin didn’t work on TB and why these new types of beta-lactam antibiotics called carbapenems do.
In collaboration with chemist John Buynak of South Methodist University in Texas, Rohde’s team will synthesize and test “next-gen” carbapenem drugs that they can optimize to target TB. The optimized antibiotics will be designed to resist enzymes the bacteria use to inactivate the drug while also destroying the bacteria’s cell wall.
Additional members of the team include Leighanne Basta, a U.S. Naval Academy biochemist and expert in the enzymes targeted by these drugs, and Konstantin Korotkov, a structural biologist with the University of Kentucky, who will create the 3D structures of the drugs and ways they can bind to their target.
The team aims to develop a potent antimycobacterial agent that can be administered orally and will test the new drug against TB and related pathogens in mice models.
“Although it can take years for new antibiotic candidates to reach patients or even clinical trials, I am optimistic that this project will yield valuable contributions to global efforts to discover new and improved treatment options for these debilitating and hard-to-treat infections,” Rohde says.