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Killing them Softly, Almost

Linda Seaton
| Oct 11, 2012

Escherichia coli.  Bacteria that are an essential part of the digestive track flora of healthy humans and most animals. Just watch out when it shows up outside that realm, where it can cause severe illness and sometimes death. The fact that multidrug resistance in E. coli has increased from just over 7% in the 1950s to more than 60% in the 2000s doesn’t help the situation. Sequencers have enabled scientists to identify the mutated E. coli genes that confer antibiotic resistance, but the resistance pathways remained a mystery.

describe the imageEnter Dr. Erdal Toprak’s team at the Department of Systems Biology at Harvard Medical School. They developed the morbidostat, a novel microbial selection device that takes bacteria (in this case E. coli) to the brink of death in the presence of antibiotics, only to let them recover just enough to mutate and develop resistance. The process is repeated over and over again. Putting five E. coli populations through this torture chamber in the presence chloramphenicol, doxycycline, and trimethoprim sequentially, yielded interesting results. In addition to identifying the multiple pathways that E. coli uses to achieve resistance to these drugs (especially chloramphenicol and doxycycline), the data also showed the speed at which the bacteria developed cross-reactivity.

The morbidostat could become a valuable tool for pharmaceutical researchers, enabling them to test antibiotic candidates to see what pathways bacteria might use to achieve resistance. Armed with this information, researchers could make modifications to the chemical compositions of these candidates to block the pathways. And the chess game continues.