Science

Novel synthetic antibiotic designed to overcome antimicrobial resistance

February 22, 2024

Harvard and University of Illinois researchers have created a fully synthetic compound antibiotic called cresomycin (CRM), which belongs to a class of antibiotics known as enhanced lincosamides and works by targeting a bacterium's protein-producing ribosome.

Although CRM isn't ready for clinical trials in humans, researchers found that when tested in mice it proved significantly more effective than currently available antibiotics in inhibiting the grown of several types of bacteria, including Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.

• In this study, researchers infected 20 mice with methicillin-resistant S. aureus. Half the mice were given 4 injections of cresomycin over 24 hours, and the other half received injections without the active ingredient. All 10 of the mice who received cresomycin were still alive 7 days after treatment. All but one of the mice who didn’t get treatment died 2 days later.
• CRM exhibited in vitro and in vivo efficacy against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains of S. aureus, E. coli, and P. aeruginosa.
• CRM also demonstrated an improved "pre-organized" ability (compared to existing drugs) to bind to bacterial ribosomes, which control protein synthesis. Although disrupting ribosomal function is a feature of many existing antibiotics, some bacteria have evolved shielding mechanisms that prevent existing drugs from working.
• Work to develop compounds like CRM through preclinical profiling studies is supported by a $1.2 million grant from Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X), a global nonprofit partnership focused on supporting the development of new antibacterial products.

Sources:

Wu Kelvin JY, et al. (2024, February 16). Science. An antibiotic preorganized for ribosomal binding overcomes antimicrobial resistance. https://pubmed.ncbi.nlm.nih.gov/38359125/

Manning, Anne J. (2024, February 15). The Harvard Gazette. Potential new weapon in battle against superbugs. https://news.harvard.edu/gazette/story/2024/02/potential-new-weapon-in-battle-against-superbugs/

Purtill, Corinne. (2024, February 15). Los Angeles Times. Could a single synthetic molecule outsmart a variety of drug-resistant bacteria? https://www.latimes.com/science/story/2024-02-15/could-a-single-synthetic-molecule-outsmart-a-variety-of-drug-resistant-bacteria