Superdrugs for Superbugs

Does evolution depend on competition or collaboration? The discovery of antibiotics saved millions of lives, yet presently world health is in avicious spiral in which bacteria rapidly evolve to defeat available classes of antibiotics. Recruiting resources and knowhow from across the globe, Prof. Roy Kishony and colleagues are returning to the genius of nature to create superdrugs for superbugs.

In a creative stroke inspired by the digital billboard for the Hollywood movie, Contagion, Kishony and his team at Technion and Harvard Medical School opened a global window to observe how bacteria evolve as they become impervious to drugs. Described in the September issue of Science, the large-scale experimental tool offered a first glimpse at bacteria adapting to increasingly higher doses of antibiotics, visible to the naked eye.

A two-by-four foot petri dish was filled with 14 liters of agar, a seaweed-derived jelly-like substance commonly used in labs to nourish organisms as they grow. The dish was divided into sections saturated with incremental doses of antibiotics. Over the course of two weeks, a camera mounted on the ceiling above the dish took periodic snapshots. The result was a direct and detailed observation of bacterial movement, death and survival: evolution at work. The headline-grabbing Microbial Evolution and Growth Arena, was called the MEGA Plate for short. The video produced by the Kishony lab was viewed over 24 million times, likely making it the most viewed scientific experiment video of all times.

According to Kishony, “Seeing bacteria spread for the first time was a thrill. Our MEGA-plate takes complex and often obscure concepts in evolution, such as mutations-selection, lineages, parallel evolution and clonal interference, and provides a visual seeing-is-believing demonstration. It is also a powerful illustration of how easy it is for bacteria to become resistant to antibiotics.” Co-investigators Michael Baym and Tami Lieberman said the images spark the curiosity of lay and professional viewers alike.

Ultimately, in a dramatic demonstration of evolved drug resistance, bacteria spread to the highest drug concentration. In the span of 10 days, bacteria produced mutant strains capable of surviving a dose of the antibiotic trimethoprim 1,000 times higher than the one that killed their progenitors. When researchers used another antibiotic (ciprofloxacin) bacteria developed 100,000-fold resistance to the initial dose.

Kishony’s lab is collaborating with Israel’s health services and with the Faculty of Computer Science to collate big data in order to develop “predictive genome-based” diagnostics capable of foreseeing bacterial evolution and provide the best treatment at the individual patient level.

Roy Kishony is the Marilyn and Henry Taub Professor of Life Sciences and Head of the Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering.



Prof. Roy Kishony, Faculty of Biology

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