The improper and extensive use of antibiotics over the past few decades has led to the emergence of antibiotic drug resistance. This phenomenon is particularly alarming in Gram-negative bacteria, including multi-drug-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Antibiotics are essential for the treatment of bacterial infections, but their effectiveness against these multi-drug-resistant bacteria has been reduced. The decline in antibiotic efficacy and the lack of new antibiotics bring us closer to the post-antibiotic era, therefore there is an urgent need to search and develop new alternative antibacterial methods to counter the serious threat posed by multi-drug-resistant bacterial infections.

Recently, researchers from the Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG) of the Singapore-MIT Alliance for Research and Technology (SMART), in collaboration with researchers from Nanyang Technological University, have identified a novel phage lysin, Abp013, as an alternative antibacterial agent to combat two of the deadliest bacteria: Acinetobacter baumannii and Klebsiella pneumoniae.

Cell lysins produced by phages have shown great potential as a new class of antibacterial agents because their properties enable them to target key structural components of the bacterial cell wall quickly and directly, and to reduce the ability of bacteria to develop drug resistance.

Over the past few decades, the improper and extensive use of antibiotics has led to the emergence of antibiotic resistance - bacterial strains develop mechanisms to resist the drugs designed to kill them. In 2019 alone, approximately 4.95 million people died from infections related to or attributed to drug resistance. Coupled with the extensive use of antibiotics during the COVID-19 pandemic, this problem has been further exacerbated, and there is an urgent need for new therapeutics against which bacteria find it difficult to develop drug resistance.

"Antibiotic resistance remains an increasingly serious threat to humanity, and more and more people die from superbug infections every year. Developing new fungicides is crucial, and cell lysins have shown great promise in treating fatal chronic wounds and lung infections." said Joash Chu, the first author of the paper and a former SMART researcher.

Cell lysins are very effective against Gram-positive bacteria, which do not have an outer lipid membrane and are therefore easily killed by cell lysins. In contrast, in Gram-negative bacteria, the presence of the outer membrane hinders the effective killing of bacteria by cell lysins. Therefore, the discovery of the novel cell lysin Abp013 is crucial for advancing therapeutic approaches against multi-drug-resistant Gram-negative pathogens.

In a paper titled "Novel Phage Lysin Abp013 against Acinetobacter baumannii" published in the journal Antibiotics, the SMART AMR team revealed their findings about the effective contact and killing of various bacterial strains by Abp013. Studies have shown that Abp013 exhibits good permeability and inactivation against multiple strains of Acinetobacter baumannii and Klebsiella pneumoniae.

Acinetobacter baumannii and Klebsiella pneumoniae are superbugs that can cause a variety of potentially life-threatening infections such as pneumonia and meningitis, especially in immunocompromised individuals. Unfortunately, many strains of these bacteria are difficult to treat because they are increasingly resistant to antibiotics. Usually, in order to treat Acinetobacter infections, medical staff must send samples for laboratory tests to determine which antibiotics can effectively combat the bacteria. Therefore, the discovery of Abp013 and its unique bacterial-targeting characteristics may facilitate the development of faster and more effective drugs targeted at these bacteria.

"Abp013 is the first Gram-negative cell lysin discovered that shows host selectivity. Before Abp013, no other cell lysin was able to target Acinetobacter baumannii and Klebsiella pneumoniae without targeting Pseudomonas aeruginosa. Understanding the mechanism behind this selectivity will help guide the development of cell lysin variants targeting different hosts." Only target the pathogenic bacteria for more precise treatment of bacterial infections," said Dr. Goh Boon Chong, the lead research scientist of SMART AMR and a co-author of the paper.

Next, the researchers will further study the crystal structure of this novel cell lysin and understand its unique underlying mechanism. This will open up the possibility of exchanging or combining the cell lysin component with other cell lysins or antibacterial components to stimulate the engineering of Gram-negative cell lysins with higher potency and to promote the development of alternative therapeutics that can resist drug resistance.