Rebuilding Antibiotics Kills Deadly Resistant Bacteria

According to the report of the American Physicists Network on August 24th, scientists at the Scripps Research Institute in the United States have successfully modified vancomycin, an important natural antibiotic, to kill mutant antibiotic-resistant bacteria. . This reconstituted antibiotic is expected to be used clinically in the future to treat patients infected with highly resistant bacteria. More importantly, the synthetic method of reconstructing antibiotics has brought hope for people to overcome many kinds of mutated resistant bacteria. The study was published on the website of the Journal of the American Chemical Society.

Clinically, vancomycin is only used when patients are infected with methicillin-resistant Staphylococcus aureus (MRSA) or are allergic to penicillin and cephalosporin. Vancomycin began to be used in the 1950s and the first drug-resistant strain was discovered in the 1980s. It can seize a necessary raw material peptidoglycan that bacteria make its cell wall, so that bacteria can not get them and die. However, mutant bacteria can express variants of peptidoglycan, change one of the key atoms, and turn an amide in the peptidoglycan formula into an ester.

The role of molecules is like a magnet. There is also attraction and repulsion. The places that once attracted the most vancomycin now make them the most repellent and they cannot recognize this mutant bacteria. What the researchers do is to control the interaction of functional molecules so that they are no longer repulsive but attract each other.

According to Dale Borg, a professor of chemistry at the Scripps Institute, this reconstituted antibiotic is a copy of the natural antibiotic vancomycin. Although the study was still in its infancy, it only designed functional molecules but showed many advances.

According to the chemical nature of the functional molecules, they changed the molecules at key positions in the vancomycin core structure. The relevant modifications are then made on the remaining 4 amino groups, such as the functional group that recognizes the variant peptidoglycan. The modified antibiotics can recapture the mutated peptidoglycans, again making it impossible for drug-resistant bacteria to obtain the raw material for making cell walls, thereby killing them. Crucially, these reconstituted antibiotics also retain the ability to bind native peptidoglycans.

Compared with the existing multi-step production process, the new method is the last step to attach the functional molecule è„’ to a single-step chemical reaction, which is the simplest and straightforward method. "From a synthetic chemistry point of view, this simplified synthesis method is also a major breakthrough," said Xie Jian, the first author of the paper and graduate student of the Boge team. This method has been proven to produce such reconstituted antibiotics on a laboratory scale.

The researchers also pointed out that this artificially reconstructed antibiotic has great potential in combating the most serious human resistant bacteria. The new study shows the direction of the development of the next generation of antibiotics for the treatment of super bacterial infections and has important clinical implications.