Sharon Shui Yee Leung
The Chinese University of Hong Kong
School of Pharmacy
Dr. Sharon Shui Yee Leung completed her PhD in Chemical Engineering at the University of Sydney in 2012. After graduation, she joined the Faculty of Pharmacy at the University of Sydney for postdoc training and focused on developing technology platforms to produce engineering particles for respiratory delivery with special interest in inhaled phage therapy. In 2018, she joined the School of Pharmacy at the Chinese University of Hong Kong. She continues her research on formulation designs to advance the science and potential application of phage and phage-encoded proteins as novel antibacterial agents. After becoming an independent researcher, Sharon has received more than 7 million HKD at the principal investigator capacity from the University Grants Committee (Hong Kong) and Hong Kong Health Bureau to support her research. To date, she has published over 80 SCI papers. She is an Associate Editor of Frontiers in Drug Delivery. She also edited a theme issue “Emerging Antibiotic Alternatives: From Antimicrobial Peptides to Bacteriophage Therapies” in Advanced Drug Delivery Reviews.
Affiliations: (1). The Chinese University of Hong Kong
Many of the WHO identified priority bacteria, including Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli, are major causative pathogens of pneumonia. It is sought-after to develop novel antibacterials and treatment strategies to combat pneumonia induced by these Gram-negative superbugs. Recently, antibacterial proteins encoded by phage, particularly endolysins and depolymerases, have emerged as novel antibacterial agents. Our team has focused on strategies to weaponize these two classes of phage-derived enzymes against lung infections induced by A. baumannii. To endow endolysins with the capability of trespassing the outer membrane (OM) barrier is believed to be the key in turning the naturally existing endolysins to antibacterial weapons against Gram-negative bacteria, including the resistant strains. We employed two different strategies, (i) protein engineering and (ii) combination treatment with colistin, to boost the OM permeability of endolysins. Enhanced antibacterial efficiency was demonstrated with an engineered lysin (LysAB2-KWK) and colistin-LysAB2 combination in vitro and in vivo using an immunocompromised mice pneumonia model. As for depolymerases, they have been widely investigated in treating bloodstream infections due to their dependency on serum-mediated bacterial killing. To extend their application to low-serum local infections, like lung infections, we reported the use of depolymerases in combination with antibiotics to achieve synergistic bacterial killing. An A. baumannii phage encoded depolymerase, Dpo71, was confirmed to be capable of potentiating seven commonly used antibiotics and reversing their bacterial resistance in the presence of 5% serum. The in vivo efficacy of a selected combination, Dpo71-ceftazidime in controlling A. baumannii-induced pneumonia was also validated in a mice model. Collectively, endolysins and depolymerases have demonstrated great potential in controlling bacterial pneumonia, but significant challenges remain in translating these novel treatments.