One-third of the world’s population is infected with a type of tuberculosis (TB) infection where the causative bacteria, M. tuberculosis (Mtb), lies in a dormant or persistent form, making it untreatable with available anti-TB drugs, according to Kate Carroll, an associate professor of chemistry at the Scripps Research Institute in Jupiter, Florida.
“The compounds we have discovered kill these persistent bacteria by disabling a major defense mechanism used by them to survive in the hostile environment of the human body,” Carroll told Vaccine News Daily. “Therefore, our compounds show tremendous promise as lead scaffolds for development of new anti-TB treatments targeting persistent Mtb."
Specifically, the compounds discovered by the Scripps team -- which includes Prakash Palde, the first author on the Scripps study -- inhibit the function of a critical enzyme responsible for survival of Mtb that is absent in humans, she said.
“This augurs well for the safety of these compounds and their analogs in the clinic,” Carroll said. “Moreover, the presence of this enzyme in other pathogenic bacteria also points to the possibility that these compounds can be developed into a class of broad-spectrum antibiotics."
Carroll said that the Scripps research team is “very excited by the potent activity of these compounds in killing the active, as well as persistent Mtb” -- so much so that the researchers have launched a plethora of studies to investigate the preclinical and clinical potential of these compounds.
“We are testing these compounds in animal models of TB infection to evaluate the efficacy of these compounds in the treatment of TB,” she said. “We are also testing the bactericidal activity of these compounds in a variety of pathogenic bacteria responsible for life-threatening diseases, such as cystic fibrosis, pneumonia and chronic urinary tract infection to evaluate the spectrum of their usage.”
And because resistance is the most common concern for anti-bacterial compounds, Carroll said the Scripps researchers also are evaluating the potential of bacteria to acquire resistance to these compounds.
“Development of new antibiotics is an arduous, lengthy and a very costly endeavor and we have just begun the journey,” she said. “Nonetheless, we know that we are on the right path.”