Nature Medicine | Spoonful of Medicine

Welcome to the morbidostat: Researchers watch deadly drug resistance in action

The word ‘morbidostat’ sounds like a death-metric — and in a way it is.

The Morbidostat, photo courtesy of Len Rubenstein

Reporting online yesterday in Nature Genetics, researchers describe a new high-tech tool termed the morbidostat that can trace the evolution of drug resistance by continuously adjusting the conditions under which bacteria grow.

The device — a web of white tubes running in and out of an incubator filled with glass vials — contains hundreds of different strains of Escherichia coli, each fed by a bundle of tubes. One tube supplies growth medium and a second delivers varying amounts of deadly antibiotic. “The device is looking all the time at how well E. coli are growing, adjusting how much antibiotic it gives,” explains study author Roy Kishony, a biophysicist at Harvard Medical School in Boston.

The machine measures the optical density of the culture — which correlates with bacterial growth — to ensure that the microbes are not completely killed by the antibiotics, but, at the same time, still facing an adaptive challenge in the face of the drugs. “The morbidostat keeps the bacteria on the edge, just suffering, but not wiped out,” says Kishony.

Challenging conditions like these promote many adaptations in succession, which could help geneticists watch evolution in action. For instance, in Kishony’s proof-of-concept study, his team conducted a 25-day continuous experiment testing resistance to one of several antibiotics in 15 parallel bacterial cultures. The researchers sequenced the E. coli populations over the course of the experiment and found far more mutations than documented previously in standard chemostat experiments, thereby opening the door to further studies about how many of these hitherto unknown mutations are involved in drug resistance.


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