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.
The research was published online this week and was supported by grant AI090810 and by NIAID contract HHSN272201000009I/01.
RE Lee et al. Spectinamides: A new class of semisynthetic anti-tuberculosis agents that overcome native drug efflux. Nature Medicine DOI: 10.1038/NM.3458 (2014).
Christine Sizemore, Ph.D., Chief, Tuberculosis, Leprosy and other Mycobacterial Diseases Branch, NIAID, is available to speak about this research.