If a malicious bacterium seems particularly hardy in the face of current treatments, it’s probably only because we haven’t discovered its secret weakness. This seems to be the prevailing ideology at Ohio State University: earlier this month we saw how deactivating a single gene starves Salmonella and renders it essentially harmless. Now OSU researchers have pinpointed a protein in E. coli that, when inhibited, causes the bacteria to explode.
E. coli is similar to Salmonella in that both are bacteria that live in the intestine, enter the body inside contaminated food, and cause unpleasant symptoms like diarrhea and vomiting. According to a Mayo Clinic article, not all strains of E. coli are harmful to the body, but those that are can usually be found in raw or undercooked vegetables and meat, especially ground beef. These harmful strains are hard to fight for the same reason that Salmonella is; namely, using antibiotics against them kills beneficial bacteria that live in the intestine and make digestion significantly more difficult.
E. coli is also a difficult target for drugs because it has two membranes, the second of which is very difficult to penetrate. A protein called MurJ has the seemingly unimportant job of flipping lipids through the inner membrane. Ohio State University professor of microbiology Natividad Ruiz studied MurJ in detail and found that it was surprisingly essential to the survival of E. coli. She and her team discovered that the flipped lipid becomes part of a cell membrane that encloses pressurized contents within the cell. Without the lipid, the membrane is too weak to hold in the pressure, and the entire cell bursts. Upon this discovery, Ruiz and her team began working on a way to suppress this protein.
(A representation of an E. coli bacterium. Note the two membranes. Image courtesy Wikimedia Commons and Togopic)
Normally, inhibiting the activity of a protein like this involves gene deactivation. But this process takes a while, perhaps too long to be useful in the case of an E. coli attack. Ruiz found that this protein could be shut down much faster, which makes it a much better weakness to exploit. “We have proof of principle that MurJ is actually a valid target because we showed that if we stop it from working, the cells will die within 10 minutes – very quickly,” she says in an OSU news release. The best part is that the prototype drug binds to chemical hotspots on the protein, rendering it useless immediately. This means that the treatment works unnaturally fast, which is perfect for quickly stopping the undesirable symptoms of E. coli.
This research was supported by funds from the American Heart Association and the National Institutes of Health. For more details on the funding for research at Ohio State University, peruse our Ohio State University Funding Report:
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