Bacteria are rapidly evolving ways to resist antibiotics, causing minor infections to become life-threatening events. Compounding the problem, new antibiotics have been incredibly challenging to develop and pharma is economically disincentivized to invest in finding them. James Martin and his colleagues Joseph Sheehan and Benjamin Bratton took on this challenge, developing an extremely potent antibiotic that targets multiple different classes of bacteria. James tells the story of identifying this antibiotic, understanding its potential, and pinpointing how its structure begets its function. Describing the state-of-the art CRISPR screens, proteomics, and machine learning methods they used, James calls for a new era of antibiotic discovery to meet the impending wave of superbugs.

About the Author

• James Martin performed this work as a graduate student in Professor Zemer Getai’s lab at Princeton University.
• James’s optimism and drive to understand a problem from all angles led him and his colleagues to develop one of the most potent antibiotics ever found.

Key Takeaways

• Our arsenal of antibiotics will soon be worthless, as bacteria evolve ways to get around their killing effects.
• Adding new antibiotics to this arsenal has been slow because they are challenging to discover and they have poor return on investment.
• Synergizing a number of new biological tools available like high throughput microscopy, CRISPR, and machine learning, new antibiotics can be developed and understood faster than ever before.
• Applying this fresh take on antibiotic discovery, a novel drug is found that targets a wide-variety of bacteria and is difficult to evolve resistance to.

Translation

• Moving this extremely potent compound to the clinic will require some smart biochemistry to make it a better drug.
• The research of James and his colleagues demonstrates a paradigm shift in how antibiotic discovery pipelines are performed to more easily and rapidly find these new drugs.

First Authors: James Martin, Benjamin Bratton, Joseph Sheehan

Paper: A Dual-Mechanism Antibiotic Kills Gram-Negative Bacteria and Avoids Drug Resistance

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