St. Jude investigators Richard Lee, Suresh Dharuman, and Gregory Phelps conducted research to address antibiotic resistance. Credit: St. Jude Children's Research Hospital
Key points:
- Researchers modified the naturally occurring antibiotic spectinomycin to create synthetic analogs that are up to 64 times more potent against Mycobecterium abscessus (Mab).
- These analogs, known as eAmSPCs, have an N-ethylene linkage structure that overcomes efflux—the main mechanism driving antibiotic resistance.
- eAmSPCs work well with various classes of antibiotics to treat Mab, meaning they should be further studied and developed as potential next-generation therapeutics.
At St. Jude Children’s Research Hospital, scientists are examining Mycobacterium abscessus (Mab) antibiotic resistance. Mab is becoming more prevalent and poses a threat to patients with compromised lung function or who are immunologically compromised.
The study, published in Proceedings of the National Academy of Science, develops a new version of the drug spectinomycin that overcomes antibiotic resistance.
Researchers modified the naturally occurring antibiotic spectinomycin to create analogs with N-ethylene linked aminomethyl spectinomycins (eAmSPCs). The synthetic eAmSPCs are up to 64 times more potent against Mab than the standard spectinomycin.
The research team also determined the mechanism of eAmSPCs efficacy. eAmSPCs circumvent efflux, which is a process that cells typically use to get rid of a drug, due to their N-ethylene linkage structure. These longer linkages modify how the antibiotic compound is pumped out of the cell to shift the balance toward higher concentrations of eAmSPC within the cell and enhanced antimicrobial efficacy.
eAmSPCs work well with various classes of antibiotics to treat Mab, meaning they should be further studied and developed. With appropriate tolerability and safety, these compounds could become next-generation therapeutics.
“It is challenging to attract pharmaceutical companies to develop new antibiotics for several economic reasons,” explained co-first author Gregory Phelps of St. Jude. “If we can boost the drug pipeline against this hard-to-treat bacteria, we can potentially make a difference for patients like the ones we have here at St. Jude who are increasingly faced with limited or no therapeutic options.”