UConn medicinal chemists have developed experimental antibiotics that kill MRSA, a common and often deadly bacteria that causes skin, lung, and heart infections, according to report in UConn Today.
The chemists found a weakness and exploited it in a way the bacteria should have trouble countering, the researchers report in the Dec. 22 issue of Cell Chemical Biology.
Cases of MRSA (Methicillin-Resistant Staphylococcus aureus) are rising and increasingly resistant to common antibiotics. The first-choice treatment for MRSA, trimethoprim-sulfamethoxazole, is relatively safe and inexpensive. But trimethoprim-resistant MRSA has begun to spread around the globe, UConn Today reported.
Medicinal chemists in the School of Pharmacy, including Dennis Wright, the late Amy Anderson and Ph.D. student Stephanie Reeve have worked to develop a drug that will be harder for MRSA to evolve resistance against. They had several candidates in the works when they asked colleagues at UConn Health and Hartford Hospital to start collecting trimethoprim-resistant strains of MRSA as test cases.
The strategic approach the chemists had taken was to target the bacteria’s use of Vitamin B9. Also known as folate, it’s as critical to MRSA bacteria. Trimethoprim is currently the only antibacterial antifolate available, and bacteria have evolved different versions of the folate enzyme that aren’t impaired by it.
But Anderson, Wright, and Reeve thought they should be able to make other, better antifolates. They analyzed the molecular structure of the enzyme they were up against, and how it needed to interact with other molecules to do its job. Only by understanding its form and function could they foil versions of the enzyme they’d never seen before, Wright said.
Armed with their knowledge, they designed new antifolates. These drugs are crafted to bind the enzyme in such a way that if the enzyme changes enough to evade them, it won’t be able to do its job with vitamin B9, either. That will hopefully make it harder for bacteria to evolve resistance. The drugs’ success against the trimethoprim-resistant strains of MRSA sampled so far bodes well, UConn Today said.
