China News Network Hefei, March 25th (Wu Lan, Yang Fan) A reporter learned from the University of Science and Technology of China on the 25th that the university's researchers have made important progress in the research of the "super bacteria" inhibition mechanism. Related research results have recently been published online in the professional journal of microbiology, "Microbiology" (mBio).

Bacteria and antibiotics are like a game of mutual rivalry. Due to the abuse of antibiotics in recent years, a class of "super bacteria" that is resistant to all β-lactam drugs (including the most commonly used penicillin and cephalosporins in the clinic)-methicillin-resistant golden grape Cocci (MRSA). Once infected with this super bacteria, it may cause deep infections such as pneumonia, sepsis, endocarditis, and even life-threatening.

The use of the inhibitor Targocil is currently considered an effective strategy against this superbug. Prof. Chen Yuxing, Prof. Zhou Congzhao and Prof. Sun Linfeng from the University of Science and Technology of China have collaborated to clarify the mechanism by which Targocil inhibits this superbug.

Fighting snakes and fighting seven inches, and fighting "super bacteria" also need to find their "seven inches" first.

Studies have shown that muramic acid, the main component of methicillin-resistant Staphylococcus aureus, is one of the key factors causing drug resistance. Muramic acid plays an important role in bacterial division, biofilm formation, host colonization, and bacterial infection. Tilting enzymes in the muramic acid synthesis pathway are important targets for new antibacterial drugs. As one of the most potential antibiotic targets, flipping enzymes and their inhibitors have become the focus of research. The small molecule Targocil of the lead compound has recently been identified as having a good inhibitory effect on this flipping enzyme, but the molecular mechanism of its inhibition is not yet clear, which is not conducive to subsequent drug development.

The research team used a cryo-electron microscopy method to analyze the mechanism of flipfase transporting muramic acid and the inhibition mechanism of Targocil, and further determined the precise site of Targocil binding flippase through biochemical experiments and computer simulations, and further verified its inhibition of flippase transport Molecular mechanism of muramic acid.

The research results will provide structural basis and theoretical guidance for the design and optimization of new antibiotics against methicillin-resistant Staphylococcus aureus.