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Researchers from the Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG) at Singapore-MIT Alliance for Research and Technology (SMART), the research firm of MIT in Singapore, have developed a method for producing customizable engineered lysines that can be used to selectively kill the bacteria of interest while leaving the others unharmed. The discovery presents a promising alternative to antibiotics for treating existing drug-resistant bacteria and bacterial infections without the risk of causing resistance.
Lysines are enzymes produced by bacteriophages to break down bacterial cells during the treatment of infections and have shown their potential as a new class of antimicrobials. One of the major benefits of lysines is that they allow for a quick and targeted kill against a specific bacterium of choice without inducing resistance.
The emergence of multidrug-resistant bacteria has also left minor bacterial infections incurable from many existing antibiotics, with at least 700,000 deaths annually from drug-resistant diseases according to the World Health Organization.
In an article titled “Engineered Lysins with Customized Lytic Activities Against Enterococci and Staphylococci” recently published in the journal Frontiers in microbiology, the SMART AMR team demonstrates one of the methods for customizing the lytic spectrum of engineered lysines.
The study reveals that SMART’s engineered lysines were able to selectively kill bacteria such as staphylococci, Enterococcus faecalis, while leaving Enterococcus faecium bacteria of the same genus intact. This is the first report of a chimeric lysine that can both target bacteria of multiple genera and selectively kill one bacterial species within one genus rather than another.
“The human body contains trillions of bacteria, which form the microbiome, and most bacteria are harmless or beneficial to us,” says AMR Research Scientist and corresponding author of the article Dr Boon Chong Goh. “What happens when we are on an antibiotic course is that the antibiotics kill all the bacteria, leaving us vulnerable to worse re-infection after we complete the antibiotic course. Because the lysines respect the microbiome and only kill the bad pathogenic bacteria, they are a very promising alternative for the treatment of bacterial infections “.
Awarded with SMART Innovation Center’s Ignition and Innovation Grants, Dr. Goh’s team has established the foundation of a technology platform by producing lysines and testing them in vitro, and is developing a range of techniques to engineer lysines.
“Because lysines are essentially proteins, they can be engineered and mass-produced,” says Ms. Hana Sakina Bte Muhammad Jai, lead author of the article and lab assistant on Dr. Goh’s team at SMART. “Our study clearly shows how modification of these proteins results in improvements in their specificity and antibacterial activities”
“In the laboratory, we have observed 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, co-first. author of the paper and laboratory technologist under Dr. Goh’s team at SMART. “While developments 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 industries would also benefit from using lysines as a targeted agent for remove unwanted bacteria from their products “.
The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore as part of its Campus for Research Excellence And Technological Enterprise (CREATE) program. The SMART AMR team also recently received the Intra-CREATE Seed Collaboration Grant to study lysines that target Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae.
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