Breakthrough Antibiotic “Cresomycin” Developed to Tackle Drug-Resistant Bacteria

Scientists from the University of Illinois Antibiotic Chicago and Harvard University have collaborated to create a groundbreaking antibiotic called cresomycin, offering a potential solution against drug-resistant bacteria. The research, published in Science, showcases cresomycin’s efficacy in suppressing pathogenic bacteria that have developed resistance to commonly prescribed antimicrobial drugs.

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Antibiotic

This innovative antibiotic represents a significant achievement in the long-standing partnership between the research groups led by Yury Polikanov, associate professor of biological sciences at UIC, and their counterparts at Harvard. The collaboration leverages UIC’s insights into cellular mechanisms and structure, crucial for designing and synthesizing new drugs.

Understanding Antibiotic Resistance

The researchers focused on the interaction between antibiotics and a common cellular target, the ribosome, and how drug-resistant bacteria modify their ribosomes to fend off attacks. Over half of all antibiotics hinder pathogenic bacteria by disrupting their protein biosynthesis, a process catalyzed by the ribosome, acting like a “3D printer that makes all the proteins in a cell.”

Many bacterial species, however, have evolved defenses by adding a methyl group to their ribosomes, disrupting antibiotic activity. The researchers, using X-ray crystallography, discovered that this defense not only physically blocks the binding site but also alters the ribosome’s internal structure, complicating antibiotic activity.

Overcoming Bacterial Defenses

To overcome this resistance, the team investigated how certain drugs, including one previously published in Nature, circumvent bacterial defenses. Using X-ray crystallography, they determined the actual structure of antibiotics interacting with drug-resistant ribosomes, providing insights for designing the new antibiotic.

Cresomycin, a synthetic antibiotic, is preorganized to avoid interference from the methyl group, attaching strongly to ribosomes and disrupting their function. The drug’s pre-optimized shape allows it to bypass bacterial defenses effectively.

Cresomycin’s Promising Potential

In animal studies at Harvard, cresomycin demonstrated protection against infections caused by multidrug-resistant strains of common pathogens like Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The next step is to assess cresomycin’s effectiveness and safety in human trials.

The success of cresomycin highlights the crucial role of structural biology in designing the next generation of antibiotics. Yury Polikanov emphasizes that without understanding the molecular mechanisms provided by structural data, developing drugs that evade resistance would be challenging.

This breakthrough antibiotic holds promise in the ongoing battle against drug-resistant bacteria, marking a significant stride in antibiotic development.