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Published on June 10, 2024
MIT Scientists Tackle Drug-Resistant Bacteria with Water-Soluble EnzymeSource: Unsplash/ Drew Hays

MIT researchers are paving the way for new antibiotics with their latest breakthrough in protein engineering. In a study published in Nature Communications, the team announced the creation of a water-soluble version of an enzyme called histidine kinase, often found in bacteria and known for being a challenging target for drug development due to its hydrophobic nature.

Histidine kinase has been on scientists' radar for its unique bacterial processes, but the difficulty of studying a hydrophobic protein outside its natural environment in the cell membrane has been a major stumbling block. By altering its structure to interact with water without losing functionality, researchers can now rapidly test potential drug interactions in hopes of identifying new antibiotics. "Each year, more than 1 million people die from antibiotic-resistant infections," said Shuguang Zhang, a principal research scientist at the MIT Media Lab and one of the senior authors of the study, highlighting the urgency of this discovery in tackling a mounting global health crisis, as reported by MIT News.

This scientific method, named the QTY code, involves substituting specific amino acids with water-attracting counterparts, a technique that could revolutionize how we approach stubborn hydrophobic proteins. "It is a great advance to be able to make functionally relevant, water-solubilized proteins," Professor William DeGrado of the University of California at San Francisco, who was not involved in the research, according to MIT News. The implications of this could stretch beyond antibiotics, offering insights into signal transports across cell membranes and potentially aiding in climate change mitigation efforts, as Zhang intends to apply this technique to transform methane into less harmful methanol.

At its core, this study opens up a promising pathway in antibiotic research. Existing drugs often target bacterial cell walls or ribosomal protein synthesis, but ignore histidine kinase, which regulates resistance and communication within bacterial cells. With no current antibiotics aimed at this protein, it represents an untapped opportunity in the fight against drug-resistant infections that continue to pose a serious threat to public health. The National Natural Science Gov. of China partially funded the study, indicating an international investment in stemming the tide of antibiotic resistance. Furthermore, artificial intelligence tools like AlphaFold complemented the research, affording a peek at the enzyme's stability when interacting with water molecules—a crucial aspect to consider when developing a drug to take down bacterial defenses.

Boston-Science, Tech & Medicine