Battling Antibiotic-resistant Microbes with Milky HAMLET
• Infections from antibiotic-resistant bacteria is a huge problem in our healthcare system. Prior to the discovery of antibiotics, bacterial infections usually meant a death sentence. But now these weapons against bacterial infections are becoming less and less effective because bacteria have evolved resistance to these drugs, thanks to widespread overuse of antibiotics in the healthcare, food and agriculture industries. It’s now become an arms race, and we seem to be on the losing side.
• Despite this problem, we don’t really have any new drugs. All we can do is re-engineer existing drugs, and obviously these drugs have the same associated resistance mechanisms. An effective, alternative strategy is to use agents to sensitize the antibiotic-resistant bacteria first, and then use the antibiotics. These sensitizing agents are known as ‘antimicrobial adjuvants’; by themselves they are not very good at killing bacteria, but when used in combination with an antibiotic, they are far more effective than the antibiotic alone.
• Researchers have found a highly effective antimicrobial adjuvant in human milk named HAMLET (Human α-lactalbumin made lethal to tumor cells). HAMLET kills bacterial cells by causing them to take up calcium through the sodium-dependent proteins on the cell membrane. This activates a cellular program that then kills the bacterial cell in a similar manner to the ‘suicide program’ known as apoptosis found in eukaryotic cells.
• By making the bacterial cells take up calcium, HAMLET specifically sensitizes them to the activity of a broad spectrum of antibiotics including methicillin. The researchers carried out these experiments on multi-drug resistant Staphylococcus aureus (including the dreaded MRSA) both in petri dishes and in experimental mice. They show that HAMLET can make many currently unusable antibiotics useful for the treatment of MRSA.
• Importantly, the researchers also showed that even after continuous growth with HAMLET, the MRSA did not become insensitive to HAMLET’s adjuvant abilities. Instead, the bacteria showed that it was unable to develop resistance to HAMLET. These results show that HAMLET is a novel antimicrobial adjuvant that can be an invaluable helper in our current arms race against antibiotic resistant bacteria.