An international team of researchers have identified an exciting new phage lysin that has demonstrated effectiveness at killing multidrug-resistant bacteria, a potentially groundbreaking step toward combatting antimicrobial resistance (AMR).
The novel lysin – called Abp013 – was discovered in a collaborative project between researchers from the Antimicrobial Resistance (AMR) Interdisciplinary Research Group (IRG) at Singapore-MIT Alliance for Research and Technology (SMART) and a team at Nanyang Technological University.
The lysin was demonstrated to be a powerful alternative antimicrobial agent against two of the most dangerous multidrug-resistance bacteria – Acinetobacter baumannii and Klebsiella pneumoniae.
Their study, titled ‘Novel Phage Lysin Abp013 against Acinetobacter baumannii’, is published in Antibiotics. The project received funding from the National Research Foundation (NRF) Singapore under its Intra-CREATE Collaborative Seed Grant.
What is a lysin?
A lysin is a type of enzyme produced by bacteriophages that have displayed strong efficacy as a new class of antimicrobials due to their properties that enable them to directly and rapidly kill structural components of a bacteria’s cell walls. This results in mitigating the bacteria’s ability to develop resistance.
The inappropriate overuse of antibiotics throughout the last few decades has caused the prevalence of AMR – a phenomenon in which strains of bacteria become immune to the effects of the medicines designed to kill them. A recent report outlined that 4.95 million people died from infections associated with AMR in 2019, highlighting the importance of developing new therapeutic agents to defeat drug-resistant bacteria, especially in the wake of the widespread antibiotic use during the COVID-19 pandemic.
Joash Chu, the first author of the research that documented the lysin discovery, and former researcher at SMART at the time of the study, said: “Antimicrobial resistance remains an ever-growing threat to humankind, and an increasing number of people die each year from superbug infections. The development of new bacteria-killing agents is crucial, and lysins have shown great promise in treating deadly chronic wound and lung infections against which no antibiotics are effective and limited treatment options are available.”
Prior studies elucidated that lysins are highly effective at combatting Gram-positive bacteria – which do not have an outer lipid membrane – causing them to be easily killed by the lysins. However, in Gram-negative bacteria, the lysins’ performance is reduced due to the presence of an outer membrane. This signifies how crucial the lysin Abp013 discovery is for advancing treatment against multidrug-resistant Gram-negative pathogens.
Combatting AMR
The team’s research found that Abp013 had excellent permeability and killing activity against multiple Acinetobacter baumannii and Klebsiella pneumoniae strains, even in complex environments where typical lysins are ineffective. Acinetobacter baumannii and Klebsiella pneumoniae are superbugs attributable to many life-threatening infections, including pneumonia and meningitis.
Treating these bacteria is becoming increasingly challenging due to their strains becoming resistant to antibiotics; for example, to treat Acinetobacter infections, clinicians need to send a specimen for laboratory testing to determine which antibiotics are effective, a time-consuming process. Nevertheless, the unique bacteria-targeting properties of the Abp013 lysin may significantly advance the development of treatments for efficient and effective targeting of these bacteria.
Dr Goh Boon Chong, Principal Research Scientist at SMART AMR, and a co-corresponding author of the paper, said: “Abp013 is the first Gram-negative lysin found to display host selectivity. Prior to the discovery of Abp013, no other lysins are capable of targeting Acinetobacter baumannii and Klebsiella pneumoniae but not Pseudomonas aeruginosa. Understanding the mechanism behind such selectivity will help guide the development of lysin variants customised to only target pathogenic bacteria, for more precise treatment of bacterial infections
The team are now working on analysing the crystal structure of the new lysin to comprehend its unique properties. This could potentially lead to merging Abp013 with other lysins or antimicrobial components to create Gram-negative lysins with superior potency, eventually making therapeutics agents that can combat AMR.
