Researchers from the Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG) at Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research company in Singapore, have developed a method to produce adaptable engineered lysines that can be used to selectively kill bacteria while keeping others unharmed. The discovery offers a promising alternative to antibiotics to treat existing drug-resistant bacteria and bacterial infections without creating the risk of resistance.
Lysines are enzymes produced by bacteriophages to break open the bacteria cells during the treatment of infections and have shown potential as a new class of antimicrobial agents. A major advantage of lysines is that they can kill quickly and in a targeted manner against a specific bacterium of your choice without generating resistance.
The emergence of multi-drug resistant bacteria has made even minor bacterial infections incurable from many existing antibiotics, with at least 700,000 deaths each year from drug-resistant diseases, according to the World Health Organization.
In a paper entitled “Engineered Lysins with Customized Lytic Activities Against Enterococci and Staphylococci,” recently published in the journal Frontiers in Microbiologythe SMART AMR team will demonstrate one of the methods to adjust the lytic spectrum of engineered lysines.
The study shows how the lysines developed by SMART were able to selectively kill bacteria such as staphylococci, Enterococcus faecalis, while leaving same-sex Enterococcus faecium bacteria unharmed. This is the first report of a chimeric lysine that can attack bacteria of multiple sexes as well as selectively kill one species of bacteria within a sex over another.
“The human body contains trillions of bacteria, which make up the microbiome, and the majority of the bacteria are either harmless or beneficial to us,” said AMR Research Scientist and corresponding paper author Dr. Boon Chong Goh. “What happens when we take a course of antibiotics is that the antibiotics kill all the bacteria, making us more vulnerable to a worse reinfection after we complete the course of antibiotics. Since lysines respect the microbiome and only eliminate the bad pathogenic bacteria,” they are a promising alternative for the treatment of bacterial infections. “
Awarded with the Ignition and Innovation Grants from the SMART Innovation Center, Dr. Goh laid the foundation for a technology platform by producing the lysines and testing them in vitro, and are developing a range of techniques to develop the lysines.
“Since lysines are essentially proteins, they can be manipulated and mass-produced,” said Ms. Hana Sakina Bte Muhammad Jai, lead author of the paper and laboratory assistant to Dr. Gosh at SMART. “Our study clearly shows how modifying these proteins translates into improvements in their specificity and antibacterial activities”
“In the lab, we have seen that once a small amount of lysine is added, it only takes 30 minutes to completely kill the bacteria, making them a very safe and efficient choice for removing unwanted bacteria,” says Ms. Linh Chi Dam , the co-lead author of the paper and laboratory technologist among Dr. Goh’s team at SMART. While advancements in custom lysine manufacturing would have a major impact on the pharmaceutical industries where lysines can be used to treat bacterial infections, the skin care and consumer care industries would also benefit from using lysines as a targeted means of eliminating unwanted bacteria. remove their products. “
The research is conducted by SMART and supported by the National Research Foundation (NRF) Singapore under the Campus for Research Excellence And Technological Enterprise (CREATE) program. The SMART AMR team also recently received the Intra-CREATE Seed Collaboration Grant to investigate lysines targeting Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae.