Bioengineered lysozyme in combination therapies for Pseudomonas aeruginosa lung infections

• Published in: Bioengineered Vol. 5; no. 2; pp. 143 - 147
• Main Authors: Griswold, Karl E, Bement, Jenna L, Teneback, Charlotte C, Scanlon, Thomas C, Wargo, Matthew J, Leclair, Laurie W
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.03.2014; Landes Bioscience
• Subjects: Addendum; Animals; Anti-Bacterial Agents - therapeutic use; antibiotics; Bioengineering - methods; biotherapeutics; Cell Survival - drug effects; cystic fibrosis; Drug Design; drug resistance; Drug Therapy, Combination - methods; lung infection model; lysozyme; lytic enzymes; Mice; Mice, Inbred C57BL; Muramidase - genetics; Muramidase - therapeutic use; Pneumonia, Bacterial - diagnosis; Pneumonia, Bacterial - drug therapy; Pneumonia, Bacterial - microbiology; protein engineering; Protein Engineering - methods; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - physiology; Pseudomonas Infections - diagnosis; Pseudomonas Infections - drug therapy; Pseudomonas Infections - microbiology; Treatment Outcome; biotherapeutics; lytic enzymes; protein engineering; lysozyme; cystic fibrosis; Pseudomonas aeruginosa; lung infection model; drug resistance; antibiotics
• DOI: 10.4161/bioe.28335
• ISSN: 2165-5979; 2165-5987

There is increasing urgency in the battle against drug-resistant bacterial pathogens, and this public health crisis has created a desperate need for novel antimicrobial agents. Recombinant human lysozyme represents one interesting candidate for treating pulmonary infections, but the wild type enzyme is subject to electrostatic mediated inhibition by anionic biopolymers that accumulate in the infected lung. We have redesigned lysozyme's electrostatic potential field, creating a genetically engineered variant that is less susceptible to polyanion inhibition, yet retains potent bactericidal activity. A recent publication demonstrated that the engineered enzyme outperforms wild type lysozyme in a murine model of Pseudomonas aeruginosa lung infection. Here, we expand upon our initial studies and consider dual therapies that combine lysozymes with an antimicrobial peptide. Consistent with our earlier results, the charge modified lysozyme combination outperformed its wild type counterpart, yielding more than an order-of-magnitude reduction in bacterial burden following treatment with a single dose.