Study finds new class of semisynthetic anti-tuberculosis agents that overcome native drug efflux
Published on January 27, 2014 at 11:40 PM
Scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have developed a method to synthesize modified forms of an established antibiotic called spectinomycin. The modified forms, unlike the original drug, can act against tuberculosis (TB) bacteria. The new compounds overcome a pump mechanism that TB bacteria ordinarily use to expel standard spectinomycin and were highly effective when tested in mice with either acute or chronic TB infection.
Richard Lee, Ph.D., of St. Jude Children's Research Hospital, Memphis, Tenn., and Anne Lenaertes, Ph.D., of Colorado State University, Fort Collins, led the research. In test tube experiments, the new compounds, collectively termed spectinamides, were narrowly targeted to TB bacteria and closely related bacteria, showed activity against multidrug-resistant and extensively drug-resistant TB bacteria, and did not harm mammalian cells. These characteristics suggest that spectinamides may work well against TB bacteria while avoiding harm to normally occurring gut bacteria.