Microfluidic Assembly of Synthetic Ecologies for Drug Discovery (MASEDD)
Abstract
We live in a world of modern medical miracles. Foremost among the greatest discoveries of modern medicine are antibiotics. Prior to the discovery of antibiotics and modern military medical care, infection and epidemic disease typically disabled or killed more combatants than the battles themselves. Antibiotics are a true modern miracle that sprang from the simple molds and soil bacteria of our world. Unfortunately, the recent and increasingly rapid rise of bacteria that are resistant to our arsenal of antibiotics has been dramatic. Without effective antibiotics no modern medicine is possible. No surgery, no chemotherapy would be possible. Warfighters, Veterans, and civilians need effective and new antibiotics to ensure the security of our military and civilian medical systems. The Story of Antibiotics Unbeknownst to most, nearly every modern antibiotic was discovered in nature from simple molds and bacteria. But why do bacteria make antibiotics? After all, antibiotics kill bacteria. The answer is simple. A species of bacteria makes antibiotics to kill off their competition. Bacteria are experts at inventing new antibiotics and have been doing this advanced chemistry for billions of years. As you might expect, if a bacteria can make a deadly poison to kill other bacteria, they also must be immune to their own poison. Thus, the rise of antibiotic resistant bacteria is simply the flipside of the bacterias exceptional ability to make new antibiotics. What if we could harness the enormous capability of bacteria to make new antibiotics by training them to work with us instead of against us? The Idea In this proposal, we are domesticating microbes to make new antibiotics using advanced microfluidic devices. Microfluidic devices are incredibly small machines that allow us to sort and move around single or small numbers of cells. The devices are not unlike small semi-conductor chips, but instead of printed circuits we print small tunnels and chambers to move cells around. The trick for any domestication, whether it is converting wolves into our happy family companions or a microbe, is to reward them for a desired ability and to breed them true. Look no further than a Dachshund to see how far we have come from the wolf. Humans have already domesticated many microbes to make cheese, yogurt, bread, beer, and wine. Our research group builds advanced micro devices that are used to train one species of bacteria (Streptomyces) that has a long and distinguished record of making antibiotics (tetracycline and daptomycin, among many others) to kill a notorious multi-drug resistant hospital Super Bug such as vancomycin- and daptomycin-resistant Enterococcus faecium. Those bacteria that succeed in killing their target are rewarded with food and breed more numerously. You might even think of it as a cage match where two bacteria enter but only one emerges. In the volume of a teaspoon we can produce millions of tiny cage matches. Generation upon generation, they hone their craft at killing the dangerous pathogens and are rewarded. At the end, we identify their strategies and the molecules they have made to kill the Super Bug. These are new leads for drug discovery. This is a radically different way of making new antibiotics that can make antibiotic discovery a sustainable process and not the product of prospecting in the wild or the lab. Many antibiotics are made by growing bacteria up in large growth vessels (akin to beer brewing). One of the most important antibiotics called daptomycin is made by growing a strain of Streptomyces. One of the most transformative outcomes from this discovery process is that we produce the very strains of bacteria that we would use to make the new antibiotics.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910679
Entities
People
- Yousif Shamoo
Organizations
- Rice University
- United States Army