New innovations from St. Jude team

For more than 100 years, antibiotics have been used to fight bacterial infection and disease. However, bacteria are increasingly developing resistance to front line antibiotics, and new therapies are needed to treat these bacterial strains.

St. Jude Children’s Research Hospital scientists have developed a second-generation antibiotic that shows early effectiveness against common bacterial infections that pose a serious health threat to children and adults.  The corresponding author is Richard Lee, Ph.D., a member of the St. Jude Department of Chemical Biology and Therapeutics.

One compound is an adaptation of an old antibiotic, spectinomycin, which is modified using structure-based drug design. The other compound is designed to treat chronic infections and biofilms caused by persister cells that have become tolerant of existing antibiotics. Small subpopulations of tolerant microbial cells are called persister cells, because they can survive the antimicrobial treatments that kill their genetically identical siblings. 
 
In treating resistant bacteria, the laboratory designed a promising new class of antibiotics, called aminomethyl spectinomycins, which follows his work on spectinomycin analogs for treating tuberculosis. In this case, a new series of spectinomycin analogs were developed for treating a broad spectrum of respiratory tract infections including S. pnuemoniae, the most common pathogenic bacteria associated with this type of infection. The aminomethyl spectinomycins are active against drug-resistant strains.

Jason Rosch, Ph.D., an assistant member in the St. Jude Department of Infectious Diseases, collaborated with Lee to demonstrate the robust efficacy of this compound series at low compound dosing levels, further validating this series. These compounds have been licensed by Microbiotx, a privately-held, clinical stage biopharmaceutical company engaged in the discovery and development of novel small molecule anti-infectives.
 
In treating tolerant bacteria, the researchers developed another set of compounds designed to treat bacteria, fungi and parasites that develop multidrug tolerance by becoming dormant. When persister cells are left behind after antimicrobial treatments, the cells become a reservoir from which an infection can recur. Examples of chronic infections include endocarditis, urinary tract infections, gingivitis, middle ear infections, fatal lung disease (cystic fibrosis) and infections produced by biofilms. These infections are often associated with implanted medical devices, such as catheters and artificial joints. Multidrug-tolerant infections account for more than 60 percent of all microbial infections, are hard to treat and are subject to infection relapse. Traditional antibiotics kill active cells via inhibition; however, this new set of compounds acts to kill dormant cells. The compounds could be used to treat infections caused by biofilms and other infections caused by chronic bacteria persister cells. These compounds have been licensed to Arietis, a Boston-based biotechnology company focused on the discovery and development of novel antimicrobial agents.